Deprecated: The each() function is deprecated. This message will be suppressed on further calls in /home/zhenxiangba/zhenxiangba.com/public_html/phproxy-improved-master/index.php on line 456
NZ719644B2 - Substituted benzamides for the treatment of arthropods - Google Patents
[go: Go Back, main page]

NZ719644B2 - Substituted benzamides for the treatment of arthropods - Google Patents

Substituted benzamides for the treatment of arthropods Download PDF

Info

Publication number
NZ719644B2
NZ719644B2 NZ719644A NZ71964414A NZ719644B2 NZ 719644 B2 NZ719644 B2 NZ 719644B2 NZ 719644 A NZ719644 A NZ 719644A NZ 71964414 A NZ71964414 A NZ 71964414A NZ 719644 B2 NZ719644 B2 NZ 719644B2
Authority
NZ
New Zealand
Prior art keywords
spp
alkyl
substituted
halogen
alkoxy
Prior art date
Application number
NZ719644A
Other versions
NZ719644A (en
Inventor
Niels Bohnke
Ulrich Gorgens
Julia Johanna Hahn
Werner Hallenbach
Tobias Harschneck
Sebastian Horstmann
Kerstin Ilg
Johannes Kobberling
Michael Maue
Hans Georg Schwarz
Original Assignee
Bayer Cropscience Aktiengesellschaft
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bayer Cropscience Aktiengesellschaft filed Critical Bayer Cropscience Aktiengesellschaft
Priority claimed from PCT/EP2014/073795 external-priority patent/WO2015067647A1/en
Publication of NZ719644A publication Critical patent/NZ719644A/en
Publication of NZ719644B2 publication Critical patent/NZ719644B2/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/14—Ectoparasiticides, e.g. scabicides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Abstract

The invention relates, inter alia, to compounds of general formula (I), where the groups A1-A4, T, n, W, Q, R1 and B1-B4 have the meanings indicated in the description. Also described are methods for producing the compounds of formula (I). The compounds of the invention are particularly suitable for controlling insects, arachnids and nematodes in agriculture and ectoparasites in veterinary medicine.

Description

SUBSTITUTED BENZAMIDES FOR THE TREATMENT OF ARTHROPODS Introduction The t application relates to trifluoro novel compounds, to processes for preparation thereof and to use thereof for controlling animal pests, in particular arthropods and especially insects, arachnids and nematodes.
It is known that ular halogen-substituted compounds have insecticidal activity (EP 1 911 751, /O69366, W02012/080376, W02012/107434 and W02012/175474).
WO 13756 ses le derivatives having insecticidal activity.
It is also known that particular halogen—substituted compounds have cytokine-inhibiting activities ().
Modern crop protection compositions have to meet many demands, for example in relation to efficacy, tence and spectrum of , and possible use. Questions of toxicity and of combinability with other active ingredients or formulation auxiliaries play a role, as does the on of the expense that the synthesis of an active ingredient requires. In addition, resistances can occur. For all these reasons, the search for novel crop protection agents can never be considered to be complete, and there is a constant need for novel compounds having properties improved over the known compounds at least in relation to individual aspects.
It was an object of the present invention to provide compounds which widen the spectrum of the ides in various aspects and/or improve their activity. [7] It has now been found that, surprisingly, particular halogen—substituted compounds and salts thereof have biological properties and are especially suitable for controlling animal pests, and therefore have particularly good usability in the agrochemical sector and in the animal health sector.
Similar compounds are already known from .
Abstract [9] Novel halogen-substituted compounds which have insecticidal, acaricidal and/or parasiticidal ty and are of the general formula (I) have been found: VVO 2015/067647 PCT/EPZOl4/07379S in which R1 is H, in each case optionally substituted C2-C6-alkeny1, C2—C6-alkynyl, C3-C7—cycloalkyl, C1-C6- alkylcarbonyl, C1-C6-alkoxycarbonyl, aryl(C1-C3)—alkyl, heteroaryl(C1-C3)-alkyl, or is ally substituted C1-C6-alkyl, preferably H or preferably C1-C2-alkyl, most preferably H or methyl, especially H, the following moieties are as follows: A1 is CR2 or N, A2 is CR3 or N, A3 is CR4 or N, is CR5 or N, is CR6 or N, is CR7 or N, is CR8 or N, is CR9 or N, and is CR10 or N, but not more than three of the A1 to A4 moieties are N and not more than three of the B1 to B5 moieties are N; R2, R3, R4, R5, R6, R7, R9 and R10 are each independently H, n, cyano, nitro, in each case optionally substituted C1-C6-alkyl, C3-C6—cycloalkyl, C1-C6-alkoxy, N—Cl—CG-alkoxyimino-Cl— C3-a1kyl, C1-C6-alkylsulphanyl, C1-C6—alkylsulphinyl, C1-C6-a1kylsulphonyl, N—Cl—Cé- alkylamino, MN—di-Cl-Cé—alkylamino or N—C1-C3-alkoxy-C1-C4—alkylamino or olidinyl; if neither of the A2 and A3 moieties is N, R3 and R4 together with the carbon atom to which they are bonded may form a 5- or ered ring containing 0, 1 or 2 nitrogen atoms and/or 0 or 1 oxygen atom and/or 0 or 1 r atom; or if neither of the A1 and A2 moieties is N, R2 and R3 together with the carbon atom to which they are bonded may form a 6-membered ring containing 0, l or 2 nitrogen atoms; ‘ R8 is halogen, cyano, nitro, in each case optionally substituted C1—C6-alkyl, C3—C6—cycloalkyl, C1- CG-alkoxy, N—C1-C6—alkoxyimino-C1-C3—alkyl, C1-C6-alkylsulphanyl, alkylsulphinyl, C1- Cé-alkylsulphonyl, N—Cl-Cé-alkylamino or NN—di-Cl-Cé-alkylamino; is O or S; is H, formyl, hydroxyl, amino or in each case optionally substituted C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3—C6—cycloalkyl, C1-C5-heterocycloalkyl, C1-C4-alkoxy, C1-C6-alkyl-C3-C6— cycloalkyl, C3-C6—cycloalkyl—C1-C6-alkyl, C6—,C10-C14—aryl, C1-C5-heteroaryl, 0—,C14-aryl- (C1-C3)-alkyl, C1-C5—heteroaryl-(C1-C3)—alkyl, N—Cl—C4-alkylamino, 4- alkylcarbonylamino, or N,N—di—C1-C4-alkylamino; or is an optionally poly-V-substituted unsaturated 6-membered carbocycle; or is an optionally poly-V-substituted unsaturated 4—, 5— or 6—membered cyclic ring, where is independently n, cyano, nitro, in each case optionally substituted C1-C5-alkyl, C1-C4- alkenyl, C1—C4-alkynyl, C3-C6-cycloalkyl, C1—C6—alkoxy, N—C1-C5-alkoxyimino-C1-C3-alkyl, C1— ylsulphanyl, C1-C6-alkylsulphinyl, C1—C6-alkylsulphonyl, or N,N—di-(C1-C6-alkyl)amino; is an optionally substituted 5-membered heteroaromatic system containing not more than 2 heteroatoms (1 or 2 heteroatoms), such as four carbon atoms and one (1) heteroatom, preferably one (1) nitrogen, one (1) oxygen or one (1) sulphur atom or three carbon atoms and two heteroatoms, preferably two nitrogen atoms, one (1) nitrogen and one (1) oxygen atom, or one (1) nitrogen and one (1) r atom, and salts, N-oxides and eric forms of the compound of the formula (I).
One aspect of the present ion relates to compounds of the formula (Ia) B// 2 \ '61 33‘\ )\ D / 2.- A1\/ A \ W R1 / \Q in which the D1, D2 moieties are each independently C-R11 or a heteroatom selected from N and O; 21522173.1:DCC -1/06/2021 the D3 and D4 moieties are each independently C or a heteroatom selected from N (i.e. the D3 and D4 moieties are each independently C or N); where not more than one (1) or two moieties selected from D1, D2, D3 and D4 is/are a heteroatom, where one (1) or two moiety ed from D1, D2, D3 and D4 is a heteroatom selected from N and O in the case of D1 and D2, or N in the case of D3 and D4; is an aromatic system; and R1, A1, A2, A3, A4, B1, B2, B3, B4, B5, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, W, Q, V, and T are each defined as described herein, where not more than one moiety selected from A1, A2, A3, A4 is N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; or where one or two moieties selected from A1, A2, A3, A4 may be N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N, and salts, N-oxides and tautomeric forms of the compounds of the formula (I). [10a] ing to a first aspect, the present invention provides a compound of the formula (Ia'') 8 B R 2 B B D 4 B 2 D 3 D D4 A 4 1 W A (Ia'') 2 A where D1 is C-R11 or a heteroatom ed from N and O; D2 is C-R11 or a heteroatom selected from N and O; D3 is C or N; D4 is C or N; D5 is C-R11 or N; 21522173.1:DCC -1/06/2021 - 4A - where not more than one (1) or two moieties selected from D1, D2, D3, D4 and D5 are a heteroatom; is an aromatic system; and R1 is H, or in each case optionally substituted C2-C6-alkenyl, C2-C6-alkynyl, C3- C7-cycloalkyl, C1-C6-alkylcarbonyl, C1-C6-alkoxycarbonyl, 1-C3)- alkyl, or heteroaryl(C1-C3)-alkyl; the following moieties are as follows: A1 is CH, A2 is CR3 or N, A3 is CR4, A4 is CH, B1 is CR6 or N, B2 is CH, B4 is CH, and B5 is CR10 or N, R3, R4, R6 and R10 are each independently H, halogen, cyano, nitro, in each case optionally substituted C1-C6-alkyl, C3-C6-cycloalkyl, C1-C6-alkoxy, N-C1-C6- alkoxyimino-C1-C3-alkyl, C1-C6-alkylsulphanyl, C1-C6-alkylsulphinyl, C1- ylsulphonyl, N-C1-C6-alkylamino, N,N-di-C1-C6-alkylamino or N-C1- C3-alkoxy-C1-C4-alkylamino or 1-pyrrolidinyl; if neither of the A2 and A3 moieties is N, R3 and R4 together with the carbon atom to which they are bonded may form a 5- or ered ring containing 0, 1 or 2 nitrogen atoms and/or 0 or 1 oxygen atom and/or 0 or 1 sulphur atom, R8 is fluorine-substituted C1-C4-alkoxy or fluorine-substituted C1-C4-alkyl; R11 is H; W is O or S; Q is H, formyl, yl, amino or in each case optionally substituted C1-C6- alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C1-C5- heterocycloalkyl, C1-C4-alkoxy, alkyl-C3-C6-cycloalkyl, C3-C6- cycloalkyl-C1-C6-alkyl, C6-,C10-C14-aryl, C1-C5-heteroaryl, C6-, C10- or C14- aryl-(C1-C3)-alkyl, C1-C5-heteroaryl-(C1-C3)-alkyl, N-C1-C4-alkylamino, NC1-C4-alkylcarbonylamino , or N,N-di-C1-C4-alkylamino; or 21522173.1:DCC -1/06/2021 - 4B (followed by page 5) - is an optionally poly-V-substituted unsaturated 6-membered ycle; or is an optionally poly-V-substituted unsaturated 4-, 5- or 6-membered heterocyclic ring, where V is ndently halogen, cyano, nitro, or in each case optionally substituted C1-C6-alkyl, C1-C4-alkenyl, C1-C4-alkynyl, C3-C6-cycloalkyl, C1-C6-alkoxy, N-C1-C6-alkoxyimino-C1-C3-alkyl, C1-C6-alkylsulphanyl, C1-C6- alkylsulphinyl, C1-C6-alkylsulphonyl, or N,N-di-(C1-C6-alkyl)amino; or a salt, N-oxide or tautomeric form thereof. [10b] ing to a second aspect, the present invention es an insecticidal composition comprising at least one compound of the formula (Ia'') according to the first aspect and an extender and/or a surface-active substance.
One embodiment of the present ion relates to compounds of the formula (Ia') 8 B R 2 B B D 4 B 2 D 3 D 11 4 A 4 1 W A (Ia') 2 A in which R1, R11, Q, W, A1, A2, A3, A4, B1, B2, B4 and B5 are each defined as described herein, where not more than one moiety selected from A1, A2, A3, A4 is N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; or where one or two moieties selected from A1, A2, A3, A4 may be N and not more than one moiety ed from B1, B2, B3, B4 and B5 is N; D1 and D2 are each independently C-R11 or a heteroatom, preferably C-R11 or a heteroatom selected from N, O and S, more preferably C-R11 or a heteroatom ed from N and O; the D3 and D4 moieties are each independently C or a heteroatom selected from N; "’0 NIB/067647 I U1 . where not more than one (1) or two moieties selected from D1, D2, D3 and D4 is/are a heteroatom, where from N and O in the one (1) or two moieties selected from D1, D2, D3 and D4 is a heteroatom selected case of D1 and D2, or N in the case of D3 and D4; is an aromatic system and R8 is as defined herein, preferably perfluorinated C1-C4-alky1.
A r embodiment of the present invention s to compounds of the formula Ga") R\(/BZ\\B18 8% )\4 /DZ~ 85 D3 -. D1 \ -‘ / [35*[34 where D1 is C-R11 or a heteroatom selected from N and 0; D2 is C—R11 or a atom selected from N and 0; D3 is C or N; D4 is C or N; D5 is OR" or N; where not more than one (1) or two moieties selected from D1, D2, D3, D4 and D5 are a heteroatom; is an aromatic system; and R1 is H, in each case ally substituted C2—C6-alkenyl, C2-C6-alkynyl, C3-C7-cycloalkyl, C1-C6-a1kylcarbonyl, C1-C6—alkoxycarbonyl, aryl(Cl-C3)-alkyl,or heteroaryl(C1~C3)- alkyl, or optionally substituted C1-C6—alkyl, more preferably H; the following moieties are as follows: A1 is CR2 or N, A; is CR3 or N, A3 is CR4 or N, A4 is CR5 or N, \N’O 2015/067647 PCT/EPZUl4-/(J73 95 B1 is CR6 or N, B is CR7 or N, B3 is CR8 or N, B4 is CR9 or N, and B5 is CR10 or N, but not more than three of the A1 to A4 moieties are N and not more than three of the B1 to B5 moieties are simultaneously N; R2, R3, R4, R5, R6, R7, R9 and R10 are each ndently H, halogen, cyano, nitro, in each case optionally substituted C1-C6-alky1, C3-C6-cycloalkyl, C1-C6—alkoxy, N-Cl—Cé- alkoxyimino—Cl-Cyalkyl, C1—C6-alkylsulphanyl, alkylsulphinyl, C1-C6- alkylsulphonyl, N—Cl-Cé-alkylamino or NN—di-Cl—Cé-alkylamino; if neither of the A2 and A3 moieties is N, R3 and R4 together with the carbon atom to which they are bonded may form a 5- or 6-membered ring containing 0, 1 or 2 nitrogen atoms and/or 0 or 1 oxygen atom and/or 0 or 1 sulphur atom, or if neither of the A1 and A2 moieties is N, R2 and R3 together with the carbon atom to which they are bonded may form a 6-membered ring containing 0, 1 or 2 nitrogen atoms; R8 is halogen, cyano, nitro, in each case optionally tuted C1-C6-alkyl, C3-C6- cycloalkyl, C1-C6-alkoxy, N-01—C6-alkoxyimino-C1-C3-alkyl, C1—C6-alkylsulphanyl, C1- C6-alkylsulphinyl, C1—C6-alkylsulphonyl, N—Cl—Cs-alkylamino or N,N-di-C1-C6- alkylamino; R11 is ndently H, n, cyano, nitro, amino or an optionally substituted C1-Cg' alkyl, C1—C5-alkyloxy, Cl-CG-alkylcarbonyl, alkylsulphanyl, C1—C6-alkylsulphinyl, C1-C6-alkylsulphonyl, preferably H; W is O or S; Q is H, formyl, hydroxyl, amino or in each case ally substituted C1-C6-alkyl, C2-C6- alkenyl, C2-C6—alkynyl, Cg-Cs-cycloalkyl, C1-C5-heterocycloalkyl, C1—C4-alkoxy, C1—C6- alkyl-C3—C6-cycloalkyl, C3—C6-cycloalkyl—C1—C6-alkyl, C6—,C10—C14-aryl, C1-C5- heteroaryl, C6-,C10-,C14-aryl-(C1—C3)-alkyl, 01—C5-heteroaryl-(C1-C3)-alkyl, N—Cl—C4— alkylamino, N—C1-C4-alkylcarbonylamino, or N,N—di—C1-C4—alkylamino; or is an optionally poly-V-substituted unsaturated 6-membered carbocycle; or \VO 2015/067647 - ~ PCT/EPZOM/(JHWS is an optionally poly—V-substituted unsaturated 4—, 5- or 6-membered heterocyclic ring, where V is independently halogen, cyano, nitro, in each case optionally tuted C1—C6-alkyl, C1-C4-alkenyl, C1-C4-alkynyl, cycloalkyl, C1-C6-alkoxy, N—Cl-Cé—alkoxyimino— C1-C3-alkyl, C1-C6-alkylsulphanyl, C1-C6-alkylsulphinyl, C1-C6—alkylsulphonyl, 0r N,N- di-(Cl-Cs-alkyl)amino; and salts, N—oxides and tautomeric forms of the compounds of the formula (Ia").
A further embodiment of the present invention relates to compounds of the formula (Ia"), where the compounds of the formula (Ia") are compounds of the formula (I-T3) B4\/J\'81 N R11 \ / B5 N \ (I-T3) in which R1, A1, A2, A3, A4, R", B1, B2, B4, B5, R8, Q and W are each defined as bed herein, where not more than one moiety selected from A1, A2, A3, A4 is N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; or where one or two moieties selected from A1, A2, A3, A4 may be N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N. id="p-14" id="p-14" id="p-14" id="p-14" id="p-14" id="p-14"
[14] A further embodiment of the present invention s to compounds of the formula (Ia"), where the compounds of the a (121") are compounds of the formula (I-T2) \VO 2015/067647 ~ 8 — in which R1, A], A3, A3, A4, R] 1, B1, B2, B4, B5, R8, Q and W are each defined as descfibed herein, where not more than one moiety selected from A1, A2, A3, A4 is N and not more than one moiety selected from B, B2, B3, B4 and B5 is N; or where one or two moieties selected from A1, A2, A3, A4 may be N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N.
A further embodiment of the t invention relates to compounds of the formula (121"), where the compounds of the formula (Ia") are compounds of the formula (I-T4) \ / R )>A4 w A \>. 1\ 46 Ai—A3_ N—Q (I—T4) in which R1, A1, A2, A3, A4, R11, B1, B2, B4, B5, R8, Q and W are each defined as described herein, where not more than one moiety selected from A1, A2, A3, A4 is N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; or where one or two moieties selected from A1, A2, A3, A4 may be N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N.
A further ment of the t invention relates to compounds of the formula (Ia"), where the compounds of the formula (Ia") are nds of the formula (I-T22) (LT-22) in which R1, A1, A2, A3, A4, R11, B1, B2, B4, B5, R8, Q and W are each defined as described herein, where not more than one moiety selected from A1, A2, A3, A4 is N and not more than one moiety WO EMS/067647 - 9 ~ PC'l‘/EP2014/073795 selected from B, B2, B3, B4 and B5 is N; or where one or two moieties selected from A], A3, A3, A4 may be N and not more than one moiety selected from B], B3, B3, B4 and B5 is N.
A further embodiment of the present invention relates to compounds of the formula (Ia"), where the compounds of the a (Ia") are compounds of the formula (I-T23) (I-T23) in which R], A1, A2, A3, A4, R", B1, B2, B4, B5, R8, Q and W are each defined as bed herein, where not more than one moiety selected from A1, A2, A3, A4 is N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; or where one or two moieties ed from A], A2, A3, A4 may be N and not more than one moiety ed from B1, B2, B3, B4 and B5 is N. id="p-18" id="p-18" id="p-18" id="p-18" id="p-18" id="p-18"
[18] A further embodiment of the present invention relates to compounds of the formulae and embodiments described herein, where R11 is independently H and W is O.
A further embodiment of the present invention s to compounds of the ae and embodiments described herein, where R11 is ndently H and W is O and B3 is C-RS, R8 is halogen- substituted C1-C3-alky1 (preferably perhalogenated C1-C3-alky1, more preferably perfluorinated C1-C3- alkyl) or halogen-substituted C1-C3-alkoxy (preferably perhalogenated C1-C3-alkoxy, more preferably perfluorinated C1-C3—alkoxy).
A further embodiment of the present invention relates to compounds of the formulae and embodiments described herein, where the A1 to A4 and B1 to B5 moieties are as follows: A1 is on, A2 is CR3 or N, A3 is CR4, A4 is C-H, B1 is CR6 or N, 32 is C-H, B3 is CR8, B4 is C-H and "’0 2015/067647 — 10 — PCT/EPZOl4/07379S B5 is CR") or N.
A further ment of the present invention relates to compounds of the formulae and embodiments described herein, where R1 is H.
A further ment of the present invention relates to compounds of the formulae and embodiments described herein, where Q is fluorine-substituted C1-C4-alky1, C3-C4-cycloalkyl, optionally cyano- or fluorine—substituted C3-C4-cycloalkyl, C4-C6-heterocycloalkyl, l-oxidothietany1, 1,1- dioxidothietan—3—yl, benzyl, pyridinylmethyl, methylsulphonyl or 2-oxo(2,2,2- roethylamino)ethyl.
A further embodiment of the present invention relates to compounds of the formulae and ments described herein, where R8 is halogen or halogen-substituted C1-C4-alkyl.
Yet a further embodiment of the present invention relates to compounds of the ae described herein, where R11 is independently H.
Yet a further embodiment of the present invention relates to compounds of the formulae bed , where R6, R7, R9 and R10 are each independently H, halogen, cyano, nitro, in each case optionally substituted C1—C4-alkyl, C3-C4-cycloalkyl, C1-C4-alkoxy, N—alkoxyiminoalkyl, C1—C4- alkylsulphanyl, C1—C4-alkylsulphinyl, C1-C4-alkylsulphonyl, N—Cl-C4-alkylamino, N,N—di-C1—C4- mino.
Yet a further ment of the present invention relates to compounds of the formulae described , where R2, R3, R4 and R5 are each independently H, halogen, cyano, nitro, in each case optionally substituted C1-C4-alkyl, C3-C4-cycloalkyl, alkoxy, N—Cl-C4-alkoxyimino-C1-C4-alkyl, C1-C4-alkylsulphanyl, C1-C4-alkylsulphinyl, C1-C4-alkylsulphonyl, N—Cl-C4-alkylamino or N,N—di—C1- C4-alkylamino.
Yet a further embodiment of the present invention relates to compounds of the formulae described herein, where the A1 to A4 and B1 to B5 moieties are as follows: A1 is C-H, A2 is CR3 or N, A3 is CR4, A4 is C—H, B1 is CR6 or N, B2 is C-H, B3 is CR8, B4 is OH and B5 is CR10 or N.
\K’O 2015/067647 — ll — PCT/EPZOl4/07379S Yet a further embodiment of the present invention relates to compounds of the formulae described herein, where R1 is H.
Yet a further embodiment of the present invention relates to compounds of the formulae described herein, where Q is C1-C4-alkyl substituted by fluorine or by carbonamide (—C(=O)N(R)2 where R is independently H, alkyl or halogen-substituted C1-C3-alkyl), optionally cyano- or fluorine-substituted C3-C4-cycloalkyl, C4-C6—heterocycloalkyl, l-oxidothietan—3-yl, 1,1-dioxidothietan yl, benzyl, pyridin-Z-ylmethyl, methylsulphonyl or 2-oxo(2,2,2-trifluoroethylamino)ethyl.
Yet a further embodiment of the present invention relates to compounds of the formulae described herein, where Q is trifluoroethyl, 2,2-difluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, cyclobutyl, cyclopropyl, cyclobutyl, l-cyanocyclopropyl, 2-fluorocyclopropyl, or cis fluorocyclopropyl, —3-yl, thietan—3-yl, othietan-3—yl, 1,1-dioxidothietan—3—yl, benzyl, pyridinylmethyl, methylsulphonyl or 2—oxo(2,2,2-trifluor0ethylamino)ethyl.
Yet a r embodiment of the present ion relates to compounds of the ae described herein, where R8 is halogen or halogen-substituted C1-C4-alkyl. id="p-32" id="p-32" id="p-32" id="p-32" id="p-32" id="p-32"
[32] A further aspect relates to insecticidal compositions, characterized by a content of at least one compound of the formula (I) as described herein and an extender and/or a surface-active substance.
A further aspect relates to a method for protecting transgenic or conventional seed and the plant that arises therefrom from infestation by pests, characterized in that the seed is treated with at least one compound of the formula (I) as bed . id="p-34" id="p-34" id="p-34" id="p-34" id="p-34" id="p-34"
[34] Yet a further aspect relates to the use of compounds of the formula (I) as bed herein or of an insecticidal composition as described herein for controlling pests.
A further aspect relates to the use of compounds of the formula (I) as described herein in vector Yet a further aspect relates to seed in which a compound of the formula (I) as described herein has been applied to the seed as a constituent of a coating or as a further layer or further layers in addition to a coating.
Accordingly, a r aspect relates to a method for applying a coating sing at least one compound of the formula (I) as bed herein or for applying a compound of the formula (I) as described herein, which is applied to seed as a layer or further layers in addition to a coating, comprising the steps of a) mixing seeds with a coating material consisting of or sing a compound of the formula (I) as described herein, b) enriching the coated seed composition obtained, 0) drying the enriched seed composition obtained, d) dis- or deagglomerating the dried seed composition obtained.
\NO 2015/0670" - 1.; » PCT/EPZUl4/(t73795 Depending on the nature of the tuents, the compounds of the formula (I) described here may optionally be in the form of ric and/or optically active isomers or corresponding isomer es in ent itions. The invention relates both to the pure isomers and to the isomer [3 9] The inventive compounds may also be in the form of metal complexes.
Definitions The person skilled in the art is aware that, if not stated explicitly, the expressions "3" or "an" as used in the present application may, depending on the situation, mean "one (1)", "one (1) or more" or "at least one (1)". id="p-41" id="p-41" id="p-41" id="p-41" id="p-41" id="p-41"
[41] For all the structures described herein, such as ring systems and groups, adjacent atoms must not be —O-O- or —O-S-.
Structures having a variable number of possible carbon atoms (C atoms) may be referred to in the present application as Clowe, limit "carbon amm-Cupper limit of carbon atom, structures (CLL—CUL ures), in order thus to be stipulated more cally. Example: an alkyl group may consist of 3 to 10 carbon atoms and in that case corresponds to C3-C10—alkyl. Ring structures composed of carbon atoms and heteroatoms may be referred to as "LL— to UL-membered" structures. One example of a 6-membered ring structure is toluene (a 6-membered ring structure substituted by a methyl group).
If a collective term for a substituent, for example (CLL-CUL)-alkyl, is at the end of a composite substituent, for example (CLL-CUL)-cycloalkyl—(CLL-CUL)-alkyl, the constituent at the start of the composite substituent, for example the (CLL—CUL)-cycloalkyl, may be mono— or polysubstituted identically or differently and ndently by the latter substituent, for example (CLL—CUL)-alkyl. All the collective terms used in this application for chemical groups, cyclic systems and cyclic groups can be stipulated more specifically through the addition "CLL—CUL" or "LL— to UL—membered".
Unless defined differently, the tion of collective terms also applies to these collective terms in composite substituents. Example: the definition of CLL-CUL—alkyl also applies to CLL-CUL-alkyl as part of a composite substituent, for example CLL-CUL-cycloalkyl—CLL-CUL—alkyl.
It will be clear to the person skilled in the art that examples cited in the present ation should not be considered in a restrictive manner, but merely describe some ments in detail.
In the definitions of the symbols given in the above formulae, collective terms which are lly entative of the following substituents were used: Halogen relates to elements of the 7th main group, preferably fluorine, chlorine, bromine and iodine, more preferably fluorine, chlorine and bromine, and even more preferably fluorine and chlorine. ""0 2015/067647 — 13 - PCT/EPZOI4/(l73795 Examples of heteroatom are N, O, S, P, B, Si. Preferably, the term "heteroatom" relates to N, S and O.
According to the invention, "alkyl" — on its own or as part of a chemical group — represents straight-chain or branched arbons ably having 1 to 6 carbon atoms, for e methyl, ethyl, n-propyl, isopropyl, n—butyl, isobutyl, s-butyl, t-butyl, pentyl, l—methylbutyl, 2-methylbutyl, 3- methylbutyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, l-ethylpropyl, hexyl, l- methylpentyl, 2-methylpentyl, 3-methylpentyl, 4—methylpentyl, l,2—dimethylpropyl, 1,3-dimethylbutyl, 1,4-dimethylbutyl, methylbutyl, l,l-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1,1,2- trimethylpropyl, 1,2,2-trimethylpr0pyl, lbutyl and 2-ethylbutyl. ence is also given to alkyls having 1 to 4 carbon atoms such as, inter alia, , ethyl, n-propyl, isopropyl, n—butyl, isobutyl, s- butyl or t-butyl. The inventive alkyls may be substituted by one or more identical or different radicals.
According to the invention, "alkenyl" — on its own or as part of a chemical group — represents straight—chain or branched hydrocarbons preferably having 2 to 6 carbon atoms and at least one double bond, for example vinyl, 2-propenyl, 2-butenyl, 3-butenyl, ylpropenyl, 2-methylpropenyl, enyl, 3-pentenyl, enyl, 1-methylbutenyl, 2-methylbutenyl, ylbutenyl, 1- methyl-3 -butenyl, 2-methylbutenyl, 3-methyl-3 -butenyl, 1,1—dimethyl-2—propeny1, 1,2-dimethyl propenyl, 1-ethylpropenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methylpentenyl, 2- methyl—2—pentenyl, 3-methylpentenyl, 4-methylpentenyl, 3-methyl—3 -pentenyl, 4-methyl pentenyl, l-methy1—4-pentenyl, 2-methylpentenyl, yl—4-pentenyl, 4—methylpentenyl, 1,1- dimethyl-2—butenyl, 1,1-dimethyl-3 -butenyl, 1,2-dimethylbutenyl, 1,2-dimethyl-3—butenyl, 1,3- dimethyl-Z-butenyl, 2,2—dimethylbutenyl, 2,3—dimethylbutenyl, 2,3-dimethyl—3-butenyl, l—ethyl butenyl, l—ethyl—3-butenyl, 2—ethylbutenyl, 2-ethyl-3—butenyl, trimethyl—2-propenyl, l-ethyl-l- methylpropenyl and l-ethyl-2—methylpropenyl. Preference is also given to alkenyls having 2 to 4 carbon atoms such as, inter alia, 2-propenyl, 2-butenyl or l-methylpropenyl. The inventive alkenyls may be substituted by one or more identical or different radicals.
According to the invention, "alkyny " — on its own or as part of a chemical group — represents straight—chain or ed hydrocarbons preferably having 2 to 6 carbon atoms and at least one triple bond, for example 2—propynyl, 2-butynyl, 3-butynyl, 1—methylpropynyl, ynyl, 3-pentynyl, 4- yl, l-methyl—3 -butynyl, 2-methyl-3 ~butynyl, 1—methy1butynyl, 1,1-dimethylpropynyl, l- ethyl-2—propynyl, 2—hexyny1, 3-hexynyl, 4-hexynyl, 5—hexynyl, l—methylpentynyl, 1-methyl—3- pentynyl, l-methylpentynyl, 2—methyl-3 -pentynyl, 2-methyl—4-pentynyl, 3-methylpentynyl, 4- methylpentynyl, 1,1-dimethylbutynyl, 1,2-dimethylbutynyl, 2,2-dimethylbutynyl, l—ethyl butynyl, 2-ethylbutynyl, lmethylpropynyl and 2,5-hexadiyny1. Preference is also given to alkynyls having 2 to 4 carbon atoms such as, inter alia, ethynyl, ynyl or nyl—2-propenyl.
The inventive alkynyls may be substituted by one or more identical or different radicals.
\WO EMS/06761.7 -1'4‘: - ZG 14/073795 According to the invention, "cycloalkyl" — on its own or as part of a al group — represents mono-, bi- or tricyclic hydrocarbons preferably having 3 to 10 carbons, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, ctyl, bicyclo[2.2.l]heptyl, bicyclo[2.2.2]octy1 or adamantyl. Preference is also given to cycloalkyls having 3, 4, 5, 6 or 7 carbon atoms such as, inter alia, ropyl or cyclobutyl. The inventive cycloalkyls may be substituted by one or more identical or different radicals. ing to the invention, "alkylcycloalkyl" represents mono-, bi- or tricyclic alkylcycloalkyl preferably having 4 to 10 or 4 to 7 carbon atoms, for example methylcyclopropyl, ethylcyclopropyl, isopropylcyclobutyl, 3-methylcyclopentyl and 4—methylcyclohexyl. Preference is also given to alkylcycloalkyls having 4, 5 or 7 carbon atoms such as, inter alia, yclopropyl or 4- methylcyclohexyl. The inventive alkylcycloalkyls may be substituted by one or more identical or different radicals.
According to the invention, "cycloalkylalkyl" represents mono—, bi- or tricyclic cycloalkylalkyl preferably having 4 to 10 or 4 to 7 carbon atoms, for example cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl and entylethyl. Preference is also given to cycloalkylalkyls having 4, 5 or 7 carbon atoms such as, inter alia, cyclopropylmethyi or cyclobutylmethyl. The inventive cycloalkylalkyls may be substituted by one or more identical or ent radicals.
According to the invention, "hydroxyalkyl" represents a straight-chain or branched alcohol preferably having 1 to 6 carbon atoms, for example methanol, ethanol, n—propanol, isopropanol, n- butanol, anol, s-butanol and t-butanol. Preference is also given to hydroxyalkyl groups having 1 to 4 carbon atoms. The inventive hydroxyalkyl groups may be substituted by one or more identical or different ls.
According to the invention, y" represents a straight-chain or branched l preferably having 1 to 6 carbon atoms, for example methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, s-butoxy and t-butoxy. Preference is also given to alkoxy groups having 1 to 4 carbon atoms. The inventive alkoxy groups may be substituted by one or more cal or different radicals.
According to the invention, "alkylsulphanyl" represents straight-chain or branched S-alkyl preferably having 1 to 6 carbon atoms, for example methylthio, ethylthio, n-propylthio, isopropylthio, n- butylthio, ylthio, lthio and t-butylthio. Preference is also given to alkylsulphanyl groups having 1 to 4 carbon atoms. The inventive alkylsulphanyl groups may be substituted by one or more identical or different radicals. [5 8] According to the invention, "alkylsulphinyl" represents straight—chain or branched alkylsulphinyl preferably having 1 to 6 carbon atoms, for example sulphinyl, ethylsulphinyl, n- propylsulphinyl, isopropylsulphinyl, n-butylsulphinyl, isobutylsulphinyl, s-butylsulphinyl and t- "’0 2015/067647 - l (JI I S butylsulphinyl. Preference is also given to alkylsulphinyl groups having 1 to 4 carbon atoms. The inventive alkylsulphinyl groups may be substituted by one or more identical or different radicals.
According to the invention, sulphonyl" represents straight-chain or branched alkylsulphonyl preferably having 1 to 6 carbon atoms, for e methylsulphonyl, ethylsulphonyl, n— propylsulphonyl, isopropylsulphonyl, n-butylsulphonyl, isobutylsulphonyl, s-butylsulphonyl and t- butylsulphonyl. Preference is also given to alkylsulphonyl groups having 1 to 4 carbon atoms. The inventive alkylsulphonyl groups may be substituted by one or more identical or different radicals.
According to the invention, "alkylcarbonyl" represents straight-chain or branched alkyl-C(=O) preferably having 2 to 7 carbon atoms such as carbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, s-butylcarbonyl and t-butylcarbonyl. Preference is also given to alkylcarbonyls having 1 to 4 carbon atoms. The inventive alkylcarbonyls may be substituted by one or more identical or different radicals.
According to the invention, "cycloalkylcarbonyl" represents straight-chain or branched cycloalkylcarbonyl preferably having 3 to 10 carbon atoms in the cycloalkyl moiety, for example cyclopropylcarbonyl, cyclobutylcarbonyl, entylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, bicyclo[2.2.1]heptyl, o[2.2.2]octylcarbony1 and adamantylcarbonyl. Preference is also given to cycloalkylcarbonyl having 3, 5 or 7 carbon atoms in the cycloalkyl moiety. The inventive cycloalkylcarbonyl groups may be tuted by one or more identical or different radicals. id="p-62" id="p-62" id="p-62" id="p-62" id="p-62" id="p-62"
[62] According to the invention, ycarbonyl" - - alone or as a constituent of a chemical group represents straight-chain or ed alkoxycarbonyl, preferably having 1 to 6 carbon atoms or having 1 to 4 carbon atoms in the alkoxy moiety, for e methoxycarbonyl, ethoxycarbonyl, n- propoxycarbonyl, isopropoxycarbonyl, s—butoxycarbonyl and t—butoxycarbonyl. The inventive alkoxycarbonyl groups may be substituted by one or more cal or ent radicals. id="p-63" id="p-63" id="p-63" id="p-63" id="p-63" id="p-63"
[63] According to the invention, "alkylaminocarbonyl" represents straight-chain or branched alkylaminocarbonyl having ably 1 to 6 carbon atoms or 1 to 4 carbon atoms in the alkyl moiety, for example methylaminocarbonyl, ethylaminocarbonyl, n—propylaminocarbonyl, isopropylaminocarbonyl, s—butylaminocarbonyl and t-butylaminocarbonyl. The inventive alkylaminocarbonyl groups may be substituted by one or more identical or different radicals. id="p-64" id="p-64" id="p-64" id="p-64" id="p-64" id="p-64"
[64] According to the invention, "N,N—dialkylaminocarbonyl" represents straight-chain or branched MN—dialkylaminocarbonyl having preferably 1 to 6 carbon atoms or 1 to 4 carbon atoms in the alkyl moiety, for example N,N—dimethylaminocarbonyl, MN—diethylaminocarbonyl, (n- propylamino)carbonyl, N,N—di(isopropylamino)carbonyl and N,N—di-(s—butylamino)carbonyl. The inventive MN—dialkylaminocarbonyl groups may be substituted by one or more identical or different radicals.
\R’CI EMS/(167647 — l6. - PCT/EPZOM/GTS79S According to the invention, "aryl" represents a mono-, bi— or polycyclic aromatic system having preferably 6 to 14, especially 6 to 10, ring carbon atoms, for example phenyl, naphthyl, anthryl, phenanthrenyl, preferably phenyl. In addition, aryl also represents polycyclic systems such as tetrahydronaphthyl, indenyl, l, fluorenyl, biphenyl, where the bonding site is on the ic system. The inventive aryl groups may be substituted by one or more identical or different radicals.
Examples of substituted aryls are the arylalkyls, which may likewise be substituted by one or more identical or different radicals in the C1—C4-alky1 and/or C6-C14-aryl moiety. Examples of such arylalkyls include benzyl and 1-phenylethyl. ing to the invention, "heterocycle", ocyclic ring" or "heterocyclic ring system" represents a carbocyclic ring system having at least one ring in which at least one carbon atom is replaced by a atom, preferably by a heteroatom from the group consisting ofN, O, S, P, B, Si, Se, and which is ted, unsaturated or heteroaromatic and may be unsubstituted or substituted, where the bonding site is on a ring atom. Unless defined ently, the heterocyclic ring contains preferably 3 to 9 ring atoms, especially 3 to 6 ring atoms, and one or more, preferably 1 to 4, especially 1, 2 or 3, heteroatoms in the heterocyclic ring, preferably from the group ting of N, O, and S, although no two oxygen atoms should be directly nt. The heterocyclic rings usually n not more than 4 nitrogen atoms and/or not more than 2 oxygen atoms and/or not more than 2 sulphur atoms. When the heterocyclyl radical or the heterocyclic ring is optionally substituted, it may be fused to other carbocyclic or heterocyclic rings. In the case of optionally substituted heterocyclyl, the invention also embraces polycyclic systems, for example 8-azabicyclo[3.2.1]octanyl or 1-azabicyclo[2.2.1]heptyl. In the case of optionally substituted heterocyclyl, the invention also embraces spirocyclic systems, for example 1-oxaazaspir0[2.3]hexyl.
Inventive heterocyclyl groups are, for example, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dihydropyranyl, tetrahydropyranyl, dioxanyl, pyrrolinyl, pyrrolidinyl, imidazolinyl, imidazolidinyl, thiazolidinyl, oxazolidinyl, dioxolanyl, yl, pyrazolidinyl, tetrahydrofuranyl, dihydrofuranyl, yl, oxiranyl, azetidinyl, aziridinyl, oxazetidinyl, idinyl, oxazepanyl, oxazinanyl, azepanyl, oxopyrrolidinyl, dioxopyrrolidinyl, oxomorpholinyl, oxopiperazinyl and oxepanyl.
Of particular cance are heteroaryls, i.e. heteroaromatic systems. According to the ion, the term heteroaryl represents aromatic compounds, i.e. completely unsaturated aromatic heterocyclic compounds which fall under the above definition of heterocycles. Preference is given to 5- to 7-membered rings having 1 to 3, preferably 1 or 2, identical or different heteroatoms from the group above. Inventive heteroaryls are, for example, furyl, thienyl, pyrazolyl, imidazolyl, 1,2,3— and 1,2,4-triazolyl, isoxazolyl,thiazoly1, isothiazolyl, 1,2,3-, 1,3,4—, 1,2,4- and 1,2,5—oxadiazolyl, azepinyl, pyrrolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, , 1,2,4- and 1,2,3—triazinyl, , 1,3,2-, "’0 2015/067647 — l7 - PCT/EPZOl4-/07379S 1,3,6- and 1,2,6—oxazinyl, oxepinyl, nyl, 1,2,4-triazolonyl and 1,2,4-diazepinyl. The inventive heteroaryl groups may also be substituted by one or more identical or different radicals.
The term "(optionally) substituted" groups/substituents, such as a substituted alkyl, alkenyl, alkynyl, alkoxy, alkylsulphanyl, alkylsulphinyl, alkylsulphonyl, cycloalkyl, aryl, phenyl, benzyl, cyclyl and heteroaryl radical, means, for e, a substituted radical derived from the unsubstituted base structure, where the substituents, for example, one (1) substituent or a plurality of substituents, preferably 1, 2, 3, 4, 5, 6 or 7, are selected from a group consisting of amino, hydroxyl, halogen, nitro, cyano, isocyano, mercapto, isothiocyanato, C1-C4-carboxyl, carbonamide, SFS, aminosulphonyl, Cl-C4- alkyl, C3-C4-cycloalkyl, C2-C4-alkenyl, C3—C4-cycloalkenyl, C2-C4-alkynyl, N—mono-Cl—C4-alkylamino, N,N—di-C1-C4-alkylamino, N—Cl-C4-alkanoylamino, C1-C4-alkoxy, C2—C4-alkenyloxy, C2-C4-alkynyloxy, C3-C4—cycloalkoxy, Cg-C4-cycloalkenyloxy, C1-C4—alkoxycarbonyl, C2-C4- alkenyloxycarbonyl, C2-C4—alkynyloxycarbonyl, 0-,C14-aryloxycarbonyl, C1-C4-alkanoyl, C2-C4-alkenylcarbonyl, C2- C4-alkynylcarbonyl, C6-,C10—,C14-arylcarb0nyl, alkylsulphanyl, C3-C4-cycloalkylsulphanyl, C1-C4- alkylthio, C2-C4-alkenylthio, C3-C4-cycloalkenylthio, C2-C4-alkynylthio, C1-C4—alkylsulphenyl and C1- C4-alkylsulphinyl, including both enantiomers of the C1-C4-alkylsulphinyl group, C1—C4-alkylsulphonyl, N—mono-C1—C4-alkylaminosulphonyl, N,N—di—C1—C4-alkylaminosulphonyl, C1-C4-alkylphosphinyl, C1- C4-alkylphosphonyl, including both enantiomers of C1-C4—alkylphosphinyl and alkylphosphonyl, N—C1—C4—alkylaminocarbonyl, N,N—di-C1-C4-alkylaminocarbonyl, N-C1-C4-alkanoylaminocarbonyl, N- alkanoyl-N-C1-C4-alkylaminocarbonyl, C6-,C10—,C14-aryl, C6-,C10-,C14-aryloxy, benzyl, benzyloxy, benzylthio, C6-,C10-,C14-arylthio, C6-,C10-,C14-arylamino, amino, heterocyclyl and trialkylsilyl, substituents bonded via a double bond, such as C1-C4-alkylidene (e.g. methylidene or ethylidene), an oxo group, a thioxo group, an imino group and a substituted imino group. When two or more radicals form one or more rings, these may be carbocyclic, cyclic, saturated, partly saturated, unsaturated, for example including aromatic rings and with further substitution. id="p-70" id="p-70" id="p-70" id="p-70" id="p-70" id="p-70"
[70] The substituents mentioned by way of example ("first substituent level") may, if they contain hydrocarbonaceous components, optionally have further substitution n ("second substituent level"), for example by one or more of the tuents each independently selected from halogen, hydroxyl, amino, nitro, cyano, isocyano, azido, acylamino, an oxo group and an imino group. The term "(optionally) substituted" group preferably embraces just one or two substituent levels. id="p-71" id="p-71" id="p-71" id="p-71" id="p-71" id="p-71"
[71] The inventive n-substituted chemical groups or halogenated groups (for example alkyl or alkoxy) are mono- or polysubstituted by halogen up to the m possible number of substituents.
Such groups are also referred to as halo groups (for example haloalkyl). In the case of polysubstitution by halogen, the halogen atoms may be the same or ent, and may all be bonded to one carbon atom or may be bonded to a plurality of carbon atoms. Halogen is especially fluorine, chlorine, bromine or iodine, preferably fluorine, ne or bromine and more preferably fluorine. More particularly, halogen—substituted groups are monohalocycloalkyl such as l-fluorocyclopropyl, Z-fluorocyclopropyl or \ — 1 G" l PC’f/EP21014/073795 1-fluorocyclobuty1, monohaloalkyl such as 2—chloroethy1, 2-fluoroethyl, 1-chloroethyl, l-fluoroethyl, chloromethyl, or fluoromethyl; perhaloalkyl such as trichloromethyl or trifluoromethyl or CFZCF3, loalkyl such as omethyl, ochloroethyl, dichloromethyl, 1,1,2,2-tetrafluoroethyl or 2,2,2-trifluoroethyl. Further examples of haloalkyls are trichloromethyl, difluoromethyl, dichlorofluoromethyl, chloromethyl, ethyl, 1-fluoroethyl, 2—fluoroethyl, 2,2-difluoroethyl, 2,2,2- trifluoroethyl, 2,2,2-trichloroethy1, 2-ch10ro-2,2-difluoroethy1, pentafluoroethyl, 3,3,3-trifluoropropyl and pentafluoro-t-butyl. Preference is given to haloalkyls having 1 to 4 carbon atoms and 1 to 9, ably 1 to 5, identical or different halogen atoms selected from fluorine, chlorine and bromine.
Particular preference is given to haloalkyls having 1 or 2 carbon atoms and 1 to 5 identical or different halogen atoms selected from fluorine and chlorine, such as, inter alia, difluoromethyl, trifluoromethyl or 2,2-difluoroethyl. r examples of n-substituted compounds are haloalkoxy such as OCF3, OCHFz, OCHzF, OCF2CF3, OCH2CF3, OCH2CHF2 and OCHZCHZCI, haloalkylsulphanyls such as difluoromethylthio, trifluoromethylthio, trichloromethylthio, chlorodifluoromethylthio, 1- fluoroethylthio, 2-fluoroethy1thio, 2,2-difluoroethylthio, 2-tetrafluoroethy1thio, 2,2,2- trifluoroethylthio or 2-chloro-1,1,2-trifluoroethy1thio, haloalkylsulphinyls such as difluoromethylsulphinyl, romethylsulphinyl, trichloromethylsulphinyl, chlorodifluoromethylsulphinyl, l-fluoroethylsulphinyl, 2-fluoroethylsulphinyl, 2,2- difluoroethylsulphinyl, 1,1,2,2-tetrafluoroethylsulphinyl, 2,2,2-trifluoroethylsulphinyl and 2-chloro— 1,1 ,2-trifluoroethylsulphinyl, haloalkylsulphinyls such as difluoromethylsulphinyl, trifluoromethylsulphinyl, trichloromethylsulphinyl, chlorodifluoromethylsulphinyl, 1- thylsulphinyl, 2-fluoroethylsulphinyl, 2,2-difluoroethylsulphinyl, 1,1 ,2,2- tetrafluoroethylsulphinyl, 2,2,2—trifluoroethylsulphinyl and 2-chloro-1,1,2-trifluoroethylsulphinyl, haloalkylsulphonyl groups such as difluoromethylsulphonyl, trifluoromethylsulphonyl, trichloromethylsulphonyl, difluoromethylsulphonyl, l-fluoroethylsulphonyl, 2- fluoroethylsulphonyl, 2,2-difluoroethylsulphonyl, 1,1,2,2-tetrafluoroethylsulphonyl, 2,2,2- trifluoroethylsulphonyl and 2-chloro—1 ,1 ,2-trifluoroethylsulphony1.
In the case of radicals having carbon atoms, preference is given to those having 1 to 4 carbon atoms, especially 1 or 2 carbon atoms. Preference is generally given to substituents from the group of halogen, e.g. fluorine and chlorine, (C1-C4)-alky1, preferably methyl or ethyl, (C1-C4)-haloalkyl, preferably trifluoromethyl, (C1-C4)-a1koxy, preferably methoxy or ethoxy, (C1—C4)-haloalkoxy, nitro and fluorine and chlorine. cyano. Particular preference is given here to the substituents methyl, methoxy, Substituted amino such as mono- or disubstituted amino means a radical from the group of the substituted amino radicals which are N-substituted, for example, by one or two identical or different ls from the group of alkyl, hydroxy, amino, alkoxy, acyl and aryl; preferably N—mono- and MN- dialkylamino, (for example methylamino, ethylamino, MN—dimethylamino, MN—diethylamino, N,N—di-n- propylamino, MN—diisopropylamino 0r MN—dibutylamino), N—mono— or MN—dialkoxyalkylamino groups (for example N-methoxymethylamino, N—methoxyethylamino, N,N-di(methoxymethyl)amino 0r N,N— \VO 2015/067647 — 19" - PCT/EPZGl4/07379S di(methoxyethyl)amino), - and MN—diarylamino, such as optionally substituted anilines, acylamino, NN—diacylainino, N—alkyl—N—arylainino, N—alkyl-N—acylamino and also saturated N- heterocycles; preference is given here to alkyl radicals having 1 to 4 carbon atoms; here, aryl is preferably phenyl or substituted phenyl; for acyl, the definition given further below applies, preferably (C1-C4)-alkanoyl. The same applies to substituted ylamino or hydrazino.
According to the invention, the term "cyclic amino groups" embraces heteroaromatic or aliphatic ring systems having one or more nitrogen atoms. The heterocycles are saturated or unsaturated, consist of one or more optionally fused ring systems and optionally contain further heteroatoms, for example one or two nitrogen, oxygen and/or r atoms. In addition, the term also embraces groups having a spiro ring or a bridged ring system. The number of atoms which form the cyclic amino group is not limited and may consist, for example, in the case of a one-ring system of 3 to 8 ring atoms, and in the case of a two-ring system of 7 to 11 atoms.
Examples of cyclic amino groups having saturated and unsaturated monocyclic groups having a nitrogen atom as heteroatom include l-azetidinyl, pyrrolidino, 2-pyrrolidin—l -yl, olyl, dino, 1,4-dihydropyrazin-l-yl, 1,2,5,6—tetrahydropyrazin—l-yl, l,4-dihydropyridin—1—yl, l,2,5,6- tetrahydropyridin—l -yl, homopiperidinyl; examples of cyclic amino groups having saturated and unsaturated monocyclic groups having two or more en atoms as atoms include 1— imidazolidinyl, l-imidazolyl, l—pyrazolyl, l-triazolyl, l-tetrazolyl, l—piperazinyl, l-homopiperazinyl, 1 ,2-dihydropiperazin-l -yl, 1 ,2—dihydropyrimidin-l -yl, perhydropyrirnidin—l -yl, l ,4-diazacycloheptan-l - yl; examples of cyclic amino groups having saturated and unsaturated monocyclic groups having one or two oxygen atoms and one to three nitrogen atoms as heteroatoms, for example, oxazolidin-3 -yl, 2,3- dihydroisoxazol-Z-yl, ol-Z-yl, 1,2,3-oxadiazin-2—yl, morpholino, examples of cyclic amino groups having saturated and unsaturated monocyclic groups having one to three nitrogen atoms and one to two sulphur atoms as heteroatoms include thiazolidinyl, isothiazolin-Z-yl, thiomorpholino, or dioxothiomorpholino; examples of cyclic amino groups having saturated and unsaturated fused cyclic groups include indol—l-yl, 1,2-dihydrobenzimidazol-l-yl, perhydropyrrolo[l,2-a]pyrazin-2~yl; examples of cyclic amino groups having spirocyclic groups include 2-azaspiro[4,5]decan—2—yl; examples of cyclic amino groups having bridged heterocyclic groups include icyclo[2.2.l]heptanyl. tuted amino also es quaternary ammonium compounds (salts) having four organic substituents on the nitrogen atom.
Optionally substituted phenyl is preferably phenyl which is unsubstituted or mono- or polysubstituted, ably up to trisubstituted, by identical or different radicals from the group of halogen, )-alkyl, (C1-C4)-alkoxy, (C1-C4)-alkoxy—(C1-C4)—alkoxy, (C1-C4)—alkoxy—(C1—C4)-alkyl, (C1-C4)—haloalkyl, (C1-C4)—haloalkoxy, (C1—C4)-alkylsulphanyl, (C1-C4)-haloalkylsulphanyl, cyano, isocyano and nitro, for example 0—, m— and p-tolyl, ylphenyls, 2-, 3— and 4—chlorophenyl, 2-, 3— \’\’O 2015/067647 - 20 — PCT/EPZGl4/O7379E and 4-fluorophenyl, 2—, 3- and 4—trifluoromethyl- and -trichloromethylphenyl, 2,4-, 3,5-, 2,5 - and 2,3- dichlorophenyl, 0-, m— and p-methoxyphenyl, 4-heptafluorophenyl.
Optionally substituted cycloalkyl is preferably cycloalkyl which is unsubstituted or mono- or polysubstituted, preferably up to trisubstituted, by identical or different radicals from the group of halogen, cyano, (Cl-C4)-alky1, (C1-C4)-alkoxy, (C1-C4)-alkoxy-(C1-C4)-alkoxy, )-alkoxy—(Cl-C4)- alkyl, (C1-C4)-haloalkyl and (Cl—C4)-haloalkoxy, especially by one or two (C1—C4)-alkyl radicals.
Optionally substituted heterocyclyl is preferably heterocyclyl which is tituted or mono- or polysubstituted, preferably up to trisubstituted, by identical or different radicals from the group of n, cyano, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C1-C4)-alkoxy-(Cl-C4)-alkoxy, (C1—C4)-alkoxy-(C1-C4)- alkyl, (C1—C4)-haloalkyl, (C1—C4)-haloalkoxy, nitro and oxo, especially mono- or polysubstituted by radicals from the group of halogen, (C1-C4)-alkyl, (C1—C4)-alkoxy, (C1-C4)-haloalkyl and oxo, most preferably substituted by one or two (C1-C4)-alkyl radicals.
Examples of alkyl-substituted heteroaryls are furylmethyl, thienylmethyl, pyrazolylmethyl, imidazolylmethyl, 1,2,3- and 1,2,4-triazolylmethyl, isoxazolylmethyl, thiazolylmethyl, isothiazolylmethyl, 1,2,3-, 1,3,4-, 1,2,4- and 1,2,5-oxadiazolylmethyl, ylmethyl, ylmethyl, pyridylmethyl, pyridazinylmethyl, pyrimidinylmethyl, pyrazinylmethyl, 1,3,5-, 1,2,4— and 1,2,3- triazinylmethyl, 1,2,4-, , 1,3,6- and 1,2,6—oxazinylmethyl, ylmethyl, thiepinylmethyl and l iazepinylmethyl.
Inventive compounds may occur in preferred embodiments. dual embodiments described herein may be combined with one r. Not included are combinations which contravene the laws of nature and which the person d in the art would ore rule out on the basis of his/her expert knowledge. Ring structures having three or more adjacent oxygen atoms, for example, are excluded.
Embodiments of the inventive compounds It will be obvious to the person skilled in the art that all the embodiments may be present alone or in ation.
The compounds of the formula (I), especially compounds of the formulae (Ia), (Ib), (I-T2), (1- T3), (I-T4), (I-T22) and (I-T23), may, where appropriate, depending on the nature of the substituents, be in the form of salts, tautomers, geometric and/or optically active isomers or corresponding isomer mixtures in different itions. id="p-84" id="p-84" id="p-84" id="p-84" id="p-84" id="p-84"
[84] Where appropriate, the inventive compounds may be in s polymorphic forms or in the form of a mixture of different polymorphic forms. Both the pure polymorphs and the polymorph mixtures form part of the subj cot—matter of the invention and can be used in accordance with the invention.
\RJO 2015/0676-1 ~ f.‘ - PCT/EPZGl4-/O7379S Embodiments of the compounds of the a (I) are described in detail below: 82 \ B B1 3‘ k A1,/ A \ w R1/ \Q in which R1 is H, in each case optionally substituted C2-C6-alkenyl, C2—C6-alkynyl, C3—C7-cycloalkyl, C1-C6- alkylcarbonyl, C1—C6-alkoxycarbonyl, aryl(C1-C3)-alky1, heteroaryl(C1-C3)-alkyl, or is optionally substituted C1-C6-alkyl, preferably H or preferably C1-C2-alkyl, most preferably H or , the following moieties are as follows: A1 is CR2 or N, A2 is CR3 or N, A3 is CR4 or N, is CR5 or N, is CR6 or N, is CR7 or N, is CR8 or N, is CR9 or N, and is CR10 or N, but not more than three of the A1 to A4 moieties are N and not more than three of the B1 to B5 moieties are aneously N; R2 R3 R4, R5, R6, R7, R9 and R10 are each independently H, halogen, cyano, nitro, in each case optionally substituted C1-C6-alkyl, C3-C6—cycloalky1, C1-C6-alkoxy, N—Cl-Cé-alkoxyimino-Cl— Cg—alkyl, C1-C6-alkylsulphanyl, C1-C6-alkylsulphinyl, C1-Cs-alkylsulphonyl, N—Cl-C6— alkylamino, MN—di-Cl-Cé-alkylamino or N—Cl—C3-alkoxy—C1-C4-alkylamino or l-pyrrolidinyl; if neither of the A2 and A3 es is N, R3 and R4 er with the carbon atom to which they are bonded may form a 5— or 6-membered ring containing 0, l or 2 nitrogen atoms and/or 0 or 1 oxygen atom and/or 0 or 1 sulphur atom, or if neither of the A1 and A2 moieties is N, R2 and R3 together with the carbon atom to which they are bonded may form a 6—membered ring containing 0, l or 2 nitrogen atoms; ""0 EMS/067647 - I: - ZGM/(l73795 R8 is halogen, cyano, nitro, in each case optionally substituted C1—C6—alkyl, C3-C6-cycloalkyl, C1— oxy, N—C1—C(,—alkoxyimino—C1-C3—alkyl, C1—C6-alkylsulphanyl, C1-C6—alkylsulphinyl, C1- C6—a1ky1sulphonyl, N—Cl-C6—alky1amino or MN—di-Cl—Cé—alkylamino; isO or S; is H, forrnyl, hydroxyl, amino or in each case optionally substituted C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalky1, C1-C5-heterocycloalkyl, C1-C4—alkoxy, alkyl-Cg-C6— cycloalkyl, C3-C6-cycloalky1-C1-C6-a1kyl, 0-C14-ary1, C1-C5-heteroary1, 0-,C14-aryl- alkyl, C1-C5-heteroary1—C1-C3-a1ky1, N—Cl-C4-alkylamino, NC4-alky1carbonylarnino, or N,N-di-C1-C4—a1kylamino; or is an optionally poly-V-substituted unsaturated 6—membered carbocycle; or is an optionally poly—V—substituted unsaturated 4—, 5— or 6-membered heterocyclic ring, where is independently halogen, cyano, nitro, in each case optionally substituted C1-C6-alkyl, C1-C4- alkenyl, C1-C4-alkynyl, C3-C6-cycloalkyl, C1-C6—alkoxy, é-alkoxyimino-C1—C3—alky1, C1- Cé-alkylsulphanyl, alkylsulphiny1, C1-C6—alky1sulphonyl, or MN—di-(Cl-Cé-alkylhmino; is an optionally substituted 5-membered heteroaromatic system containing not more than 2 heteroatoms, such as four carbon atoms and one (1) heteroatom, preferably one (1) nitrogen, one (1) oxygen or one (1) sulphur atom or three carbon atoms and two heteroatoms, preferably two en atoms, one (1) nitrogen and one (1) oxygen atom, or one (1) nitrogen and one (1) sulphur atom, and salts, N—oxides and tautomeric forms of the compounds of the formula (I).
In a preferred embodiment, R1 in a nd of the formula (I) is H, in each case optionally substituted methyl, ethyl, n—propyl, isopropyl, l, isobutyl, s-butyl, t—butyl, methoxymethyl, ethoxymethyl, propoxymethyl, methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, s- butylcarbonyl, t—butylcarbonyl, methoxycarbonyl, ethoxycarbonyl, n—propoxycarbonyl, isopropoxycarbonyl, s-butoxycarbonyl, t-butoxycarbonyl, cyanomethyl, 2—cyanoethyl, benzyl, 4— methoxybenzyl, pyrid-Z-ylmethyl, pyrid—3—y1methyl, pyridylmethyl, 4-chloropyridy1methy1.
In an even more preferred embodiment, R1 is H. id="p-88" id="p-88" id="p-88" id="p-88" id="p-88" id="p-88"
[88] In a r preferred embodiment, W is O.
VVO 2015/06764—7 - k.) L» I In a further preferred ment, Q is H, in each case optionally substituted methyl, ethyl, n- propyl, l-methylethyl, 1,1—dimethylethyl, l—methylpropyl, n-butyl, 2-methylpropyl, 2-methylbutyl, hydroxymethyl, 2-hydroxypropyl, ethyl, 2-cyanoethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2- trifluoroethyl, l-trifluoromethylethyl, 2,2—difluoropropyl, 3,3,3-trifluoropropyl, 2,2—dimethyl-3— fluoropropyl, cyclopropyl, l-cyanocyclopropyl, 1—methoxycarbonylcyclopropyl, l-(N- methylcarbamoy1)cyclopropyl, l~(N-cyclopropylcarbamoyl)cyclopropyl, 1-(thiocarbamoyl)cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, l-cyclopropylethyl, bis(cyclopropyl)methyl, 2,2—dimethylcyclopropylmethyl, 2-phenylcyclopropyl, chlorocyclopropyl, trans chlorocyclopropyl, cischlorocyclopropyl, 2,2-difluorocyclopropyl, transfluorocyclopropyl, cis fluorocyclopropyl, transhydroxycyclohexyl, 4-trifluoromethylcyclohexyl, prop-Z-enyl, ylprop- 2—enyl, propynyl, 1,1-dimethylbutynyl, 3-chloropropenyl, 3,3-dichloropropenyl, 3,3- dichloro-l,l—dimethylprop—Z—enyl, phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, oxetan—S-yl, thietany1, 1-oxidothietan—3—yl, oxidothietan—3-yl, olylmethyl, 2—oxo-2—(2,2,2— trifluoroethylamino)ethyl, 1,2,4—triazol-3 -y1methyl, yloxetan—3 -ylmethyl, benzyl, 2,6- difluorophenylmethyl, ophenylmethyl, 2-fluorophenylmethyl, 2,5-difluorophenylmethyl, l- phenylethyl, rophenylethyl, 2-trifluoromethylphenylethyl, l-pyridin-Z-ylethyl, pyridin-Z- ylmethyl, 5-fluoropyridinylmethyl, oropyridin-3 -yl)methyl, pyrimidin—Z—ylmethyl, methoxy, 2- ethoxyethyl, 2-(methylsulphanyl)ethyl, l-methyl(ethylsulphanyl)ethyl, 2—methyl-l - (methylsulphanyl)propan—2-y1, ycarbonyl, methoxycarbonylmethyl, NHZ, N-ethylamino, N- allylamino, MN—dimethylamino, N,N—diethylamino; or Q is one of the following, each substituted by 0-4 V substituents: phenyl, naphthyl, pyridazine, pyrazine, dine, triazine, pyridine, pyrazole, thiazole, isothiazole, oxazole, isoxazole, triazole, imidazole, filran, thiophene, pyrrole, oxadiazole, thiadiazole, where V is independently F, Cl, Br, I, cyano, nitro, methyl, ethyl, omethyl, trichloromethyl, chlorodifluoromethyl, dichlorofluoromethyl, trifluoromethyl, chloromethyl, bromomethyl, l-fluoroethyl, Z-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, l,2,2,2-tetrafluoroethyl, l-chloro-l,2,2,2- tetrafluoroethyl, 2,2,2-trichloroethyl, 2-chloro-2,2-difluoroethyl, 1,1-difluoroethyl, pentafluoroethyl, uoro—n—propyl, heptafluoroisopropyl, nonafluoro-n-butyl, cyclopropyl, cyclobutyl, y, 3O ethoxy, n—propoxy, l—methylethoxy, fluoromethoxy, difluoromethoxy, chlorodifluoromethoxy, rofluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2,2—difluoroethoxy, pentafluoroethoxy, N—methoxyiminomethyl, l-(N-methoxyimino)ethyl, methylsulphanyl, methylsulphonyl, methylsulphinyl, trifluoromethylsulphonyl, trifluoromethylsulphinyl, romethylsulphanyl, N,N—dimethylamino. id="p-90" id="p-90" id="p-90" id="p-90" id="p-90" id="p-90"
[90] In a further preferred embodiment, Q is optionally substituted C1-C4-alkyl or optionally substituted C3-C6—cycloalkyl or an unsaturated 4-, 5- or 6-membered cyclic ring optionally "’0 2015/067647 - 24 — substituted by one, two or three V substituents, where V is independently halogen, cyano, nitro, oxo (=0), optionally n—substituted C1—C6-alkyl, alkenyl, C1—C6—alkoxy, C1-C6-alkylsulphanyl, C1—C6—alkylsulphinyl, C1-C6-alkylsulphonyl. Preferably, Q is halogen-substituted C1-C3-alkyl; with R is independently H or C1-C3-alkyl, substituted cyano, hydroxyl or carbonamide (—C(=O)N(R)2 where C1-C3-a1kyl; C3-cycloalkyl; cyano-substituted, halogen-substituted, nitro—substituted or halogenated C1- CZ-alkyl-substituted C3-cycloalkyl; an rated 4-, 5- or 6-membered heterocyclic ring ally substituted by one, two or three V and containing one or two heteroatoms selected from a group consisting of N, O and S, where V is ndently halogen, cyano, nitro, 0x0 (=0), optionally halogen- substituted C1-C6-alkyl. More preferably, Q is fluorinated C1-C3-alkyl such as CF3, CHZCF3 or CHch2CF3; C1-C3-alkyl substituted by carbonamide (—C(=O)N(R)2 where R is independently H, C1-C3- alkyl or halogen-substituted C1-C3-alkyl, such as 2-oxo—2—(2,2,2—trifluoroethylamino)ethyl; cyclopropyl; cyano-substituted or fluorinated C1—C2-alkyl-substituted cyclopropyl such as no)cyclopropyl or 1- oromethyl)cyclopropyl); a 4-membered heterocyclic ring containing one heteroatom selected from a group consisting of N, O and S, such as thietan—3 —yl. id="p-91" id="p-91" id="p-91" id="p-91" id="p-91" id="p-91"
[91] In a more preferred embodiment, Q is fluorine-substituted C1-C4-alky1 such as 2,2,2- trifluoroethyl, 2,2-difluoroethyl, 3,3,3-trifluoropropyl; C3-C4-cycloalkyl such as cyclopropyl or cyclobutyl; optionally tuted C3-C4—cycloalky1 such as l-trifluoromethylcyclopropyl, 1—tert- butylcyclopropyl, l-thiocarbamoylcyclopropyl, 1—cyanocyclopropyl, transfluorocyclopropy1, cis fluorocyclopropyl; C4-C6—heterocycloalkyl such as oxetan-S-yl, thietan—3-yl, 1-oxidothietan-3 -yl or 1,1- dioxidothietan-3 -yl; benzyl; pyridin—Z-ylmethyl; methylsulphonyl; or 2-oxo(2,2,2— trifluoroethylamino)ethy1.
In a particularly preferred embodiment, Q is fluorine-substituted C1-C3-alkyl such as 2,2,2- roethyl or 3,3,3-trifluoropr0pyl; cyclopropyl; ally substituted cyclopropyl such as l- cyanocyclopropyl or 1-trifluoromethylcyclopropyl, thietan—3 -yl; or 2—0x0-2—(2,2,2- trifluoroethyl)aminoethyl.
A1 to A4 In a preferred embodiment, not more than one (1) A1 to A4 moiety is N (in other words: one (1) A1 to A4 (preferably A2) is N); or no (0) A1 to A4 is N (in other words: A1 to A4 are each CR2, CR3, CR4, and CR5); or one or two moieties selected from A1, A2, A3, A4 may be N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N.
In a further preferred embodiment, R2, R3, R4 and R5 (if the corresponding A moiety is CR) in a compound of the a (I) are each independently H, halogen, cyano, nitro, in each case ally substituted C1-C4-alkyl, C3—C4-cycloalkyl, alkoxy, N—C1-C4-alk0xyimino—C1-C4-alkyl, C1-C4- alkylsulphanyl, C1—C4-alkylsulphinyl, C1—C4-alkylsulphony1, N—Cl-C4—alkylamino, MN—di-Cl—C4- alkylamino or N—C1—C3-alkoxy-C1-C4—alkylamino or l—pyrrolidinyl. — 25 - PCT/EPZOl4/O7379S In a further preferred embodiment, R2 and R5 are each independently H, methyl, F and Cl.
In a further preferred embodiment, R3 and R4 are each independently H, F, Cl, Br, I, cyano, nitro, methyl, ethyl, fluoromethyl, difluoromethyl, chlorodifluoromethyl, trifluoromethyl, 2,2,2- trifluoroethyl, methoxy, ethoxy, n-propoxy, 1-methylethoxy, fluoromethoxy, difluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 2—chloro-2,2- difluoroethoxy, uoroethoxy, N-methoxyiminomethyl, l-(N-methoxyimino)ethyl, methylsulphanyl, trifluoromethylsulphanyl, methylsulphonyl, methylsulphinyl, trifluoromethylsulphonyl, trifluoromethylsulphinyl.
B1 to B5 id="p-97" id="p-97" id="p-97" id="p-97" id="p-97" id="p-97"
[97] In a preferred embodiment, not more than one (1) B1 to B5 moiety is N (in other words: one (1) B1 to B5 is N); or no (0) B1 to B5 is N (B1 to B5 are each CR6, CR7, CR8, CR9 and CR").
In a further preferred embodiment, R6, R7, R9 and R10 (when the corresponding B moiety is CR) are each independently H, halogen, cyano, nitro, in each case ally substituted C1—C4-alkyl, C3-C4— cycloalkyl, C1-C4-alkoxy, xyiminoalkyl, C1-C4—alkylsulphanyl, C1-C4-alkylsulphinyl, C1-C4— ulphonyl, 4-alkylamino, N,N—di-C1—C4-alkylamino.
In a r preferred embodiment, R6, R7, R9 and R10 are each independently H, halogen, cyano, nitro, methyl, ethyl, fluoromethyl, difluoromethyl, chlorodifluoromethyl, trifluoromethyl, 2,2,2— trifluoroethyl, methoxy, ethoxy, n-propoxy, l-methylethoxy, ethoxy, difluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy, trifluoromethoxy, 2,2,2—trifluoroethoxy, 2—chloro-2,2- difluoroethoxy, pentafluoroethoxy, N—methoxyiminomethyl, 1-m—methoxyimino)ethyl, methylsulphanyl, trifluoromethylsulphanyl, methylsulphonyl, methylsulphinyl, trifluoromethylsulphonyl, romethylsulphinyl.
In a further preferred embodiment, R6 and R10 are each independently H, halogen ially chlorine, bromine, fluorine), cyano, nitro, methyl, ethyl, difluoromethyl, difluoromethyl, trifluoromethyl, y, ethoxy, l—methylethoxy, difluoromethoxy, difluoromethoxy, dichlorofluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 2-chloro—2,2-difluoroethoxy, methylsulphanyl, trifluoromethylsulphanyl, methylsulphonyl, methylsulphinyl, trifluoromethylsulphonyl, trifluoromethylsulphinyl.
In a further preferred embodiment, R6 and R10 are the substituents described herein, but R6 and R10 in one compound are not both H. In other words, when R6 in a compound is H, R10 is one of the other substituents described herein, and Vice versa. "’0 2015/067647 2014/073795 In a further preferred embodiment, R6 and R10 are each a tuent ed from halogen (preferably Cl, Br or F), alkyl, halogen—substituted C1-C3—alkyl, C1-C3-alkoxy and halogen- substituted C1-C3-alkoxy.
In a further preferred embodiment, R6 and R10 are each halogen (such as Cl, Br or F), are each C1-C3-alkyl, or are each halogen-substituted C1-C3-alkyl, for example perfluorinated C1-C3-alkyl (perfluoromethyl, perfluoroethyl or perfluoropropyl).
In a further preferred embodiment, R6 is rinated alkyl (e. g. perfluoromethyl) and R10 is Cl, Br or F, more preferably C1 or Br. id="p-105" id="p-105" id="p-105" id="p-105" id="p-105" id="p-105"
[105] In a particularly preferred embodiment, B3 is C-R8 in which R8 is halogen, cyano, nitro, halogen—substituted C1—C4-alkyl, C3-C4—cyc10alkyl, C1-C4-alkoxy, N—C1—C4-alkoxyimino-C1—C4-alkyl, C1- C4-alky1sulphanyl, C1—C4-alkylsulphinyl, C1-C4-alkylsulphonyl, N—Cl—C4-alkylamino or N,N—di-C1-C4- alkylamino.
In a further preferred embodiment, R8 is halogen such as fluorine, chlorine, bromine, iodine, or halogen-substituted C1—C4-alkyl, cyano, nitro, methyl, ethyl, omethyl, oromethyl, difluoromethyl, dichlorofluoromethyl, trifluoromethyl, chloromethyl, bromomethyl, l—fluoroethyl, 2-fluoroethyl, 2,2—difluoroethyl, 2,2,2-trifluoroethyl, 1,2,2,2—tetrafluoroethyl, 1-chloro-1,2,2,2- tetrafluoroethyl, 2,2,2—trichlor0ethyl, 2-chloro-2,2-difluoroethyl, 1,1-difluoroethy1, pentafluoroethyl, pentafluoro—tert-butyl, heptafluoro-n-propyl, heptafluoroisopropyl, nonafluoro-n—butyl, nonafluoro-sec- butyl, ropyl, cyclobutyl, y, ethoxy, n-propoxy, 1—methylethoxy, fluoromethoxy, difluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy, trifluoromethoxy, 2,2,2- trifluoroethoxy, 2—chloro—2,2-difluoroethoxy, pentafluoroethoxy, N—methoxyiminomethyl, 1-(N— methoxyimino)ethyl, methylsulphanyl, methylsulphonyl, sulphinyl, trifluoromethylsulphonyl, trifluoromethylsulphinyl, trifluoromethylsulphanyl, N,N-dimethylamino. id="p-107" id="p-107" id="p-107" id="p-107" id="p-107" id="p-107"
[107] In a more preferred embodiment, R8 is difluoromethyl, trichloromethyl, chlorodifluoromethyl, dichlorofluoromethyl, trifluoromethyl, l-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2- trifluoroethyl, 1,2,2,2—tetrafluoroethyl, 1—chloro-1,2,2,2-tetrafluoroethyl, 2,2,2-trichloroethyl, 2-chlor0- 2,2-difluoroethyl, 1,1-difluoroethyl, pentafluoroethyl, pentafluoro—tert-butyl, heptafluoro—n-propyl, heptafluoroisopropyl, nonafluoro—n-butyl, nonafluoro-sec-butyl, fluoromethoxy, omethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2,2— difluoroethoxy, pentafluoroethoxy, trifluoromethylsulphonyl, trifluoromethylsulphinyl, trifluoromethylsulphanyl.
Vx’O 2015/067647 S In a further more preferred embodiment, R8 is halogen-substituted C1—C3-alkyl (preferably perfluorinated C1-C3-alkyl (CF3, C2135 or C3F7)) or n-substituted alkoxy (preferably perfluorinated C1—C3-a1koxy (OCF3, OC2F5 or OC3F7)).
In a particularly preferred embodiment, R8 is perfluorinated a1ky1 such as perfluorinated n— or i-propyl (-C3F7), perfluorinated ethyl (CZFS) or perfluorinated methyl (CF3), more preferably perfluorinated n— or i-propyl (-C3F7) or perfluorinated methyl.
A andB In a further red embodiment, the A1 to A4 and B1 to B5 moieties in compounds of the formula (I) are as follows: A1 iS C-H, A2 is CR3 or N, A3 is CR4, A4 is CR5 or N, B1 is CR6 or N, B2 is CR7, B3 is CR8, B4 is CR9 and B5 is CR10 or N.
In an even more preferred embodiment, the A1 to A4 and B1 to B5 moieties in compounds of the formula (I) are as follows: A1 is C—H, A2 is CR3 or N, A3 is CR4, A4 is C-H, B1 is CR6 or N, 32 is C-H, B3 is CR8, B4 is C-H and B5 is CR") or N. id="p-112" id="p-112" id="p-112" id="p-112" id="p-112" id="p-112"
[112] In an even more preferred embodiment, the A1 to A4 and B1 to B5 moieties in nds of the a (I) are as follows: A1 is C—H, PCT/EP2014/O73795 A2 is CR3 or N, A3 is CR4, A4 is C-H oder N, 131 is CR6, B2 is C-H, B3 is CR8, B4 is C-H and B5 is CR10 or N. id="p-113" id="p-113" id="p-113" id="p-113" id="p-113" id="p-113"
[113] In a further preferred embodiment, T is one of the 5-membered heteroaromatic systems shown below, where the bond to the carbon atom of the (C-Bl-Bs) ring system is fied by a dotted bond marked with an asterisk, and the bond to the carbon atom of the (C—Al-Ag-Ag—C-A4)-ring system by a dotted bond.
R11 R11 H HR11 R11 \|\\| / \ s N, N a N/ \ R11R11 T1 T2 T3 T4 O——\R H Fi//‘*O R11 11 T5 T8 T9 T10 T12 T13 T14 ‘WO 67647 Rm\ 1R 1R W N N 1R 1R \ / . \ ,.. / ~ .. N N * * / \ / \ H AI. ..* ..* R R O O T15 T16 T18 T19 T20 T21 T22 T23 1R 1R R N N S / \ / \ \ / ..* \ 1 ..* S S N N T24 T25 T26 T27 Rn\ R12 N/_S A? N\ ._N N\ 1*" / \ ,. .1. _* x H H H R R R R11 T28 T29 T30 T31 1R AIR Rm\ 1R N/ 1R Q \ / N\ R N N /N \ w * / . \ N / \ * u -.|K N NIR NIR W.
T32 T33 T34 T35 \VO 2015/067647 — 30 — I’CT/EI’2014/07379S T45 T46 T47 where R11 is independently H, n, cyano, nitro, amino or an optionally substituted C1—C6-alkyl, C1-C6- alkyloxy, C1-C6—alkylcarbonyl, C1-C6-alkylsulphanyl, C1-C5-alky1sulphinyl, C1-C6-alkylsulphonyl, preferably H; and R12 is H, halogen, cyano, nitro, amino or an optionally substituted C1-C6-alkyl, C1—C6-alkyloxy, C1-C6- arbonyl, C1-C6-alkylsulphanyl, C1-C6—alkylsulphinyl, C1-C6-alkylsulphonyl, preferably H or methyl.
In a further preferred embodiment, R11 is independently halogen, cyano, nitro, amino, methyl, ethyl, l-methylethyl, tert-butyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, 2,2-difluoroethoxy, trifluoroethoxy, methylcarbonyl, ethylcarbonyl, trifluoromethylcarbonyl, methylsulphanyl, sulphinyl, methylsulphonyl, tn'fluoromethylsulphonyl, trifluoromethylsulphanyl or trifluoromethylsulphinyl.
In a more preferred embodiment, R11 is ndently H, methyl, ethyl, 2-methylethyl, 2,2- dimethylethyl, fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl or amino.
In a further preferred embodiment, T is one of the 5-membered heteroaromatic systems shown below, where the bond to the carbon atom of the (C-Bl-Bs) ring system is identified by a dotted bond marked with an asterisk, and the bond to the carbon atom of the (C-Al—Az-A3-C-A4)-ring system by a dotted bond. 11 R R11 11 R11 11 N N R R \ \ *‘"N \ >( /~ \ N.
\ ‘ *---N\ / *--— \ \ N~ N \ N/ \ R11 R11 T1 T2 T3 T4 Vx’O 2015/067647 PCT/EP2014-/073795 R11 R11\ R11 *"fl[o\N O ‘ \N\ T * ‘ fir T18 T19 T20 0—K] [7—8 R11 R11 T22 T23 T28 T29 11 R11 R11 R11 R11 *.—-NW/)‘\ N / L In a more preferred ment, T is one of the S-membered heteroaromatic systems shown below, where the bond to the carbon atom of the (C-Bl-Bs) ring system is identified by a dotted bond marked with an asterisk, and the bond to the carbon atom of the (C-Al-Az-Ag—C-A4)-ring system by a dotted bond. 11 R11 R11 /N\ ‘Nx *'"N *"" \ \ / N.~~ \ /N~.~ R11 R11 T2 T3 T4 x~/ *"fl%)\~O‘R‘ Ale-"82‘"'7-8 *"’K\2"‘Sci 11 R11 R11 R11 T22 T23 T28 T29 "’0 2015/067647 — 37’ — T45 T46 T47 where R11 is defined as described herein and n has the values of 1 or 2.
In a particularly preferred embodiment, T is one of the 5-membered heteroaromatic systems shown below, where the bond to the carbon atom of the (C—Bl-Bs) ring system is identified by a dotted bond marked with an asterisk, and the bond to the carbon atom of the (C-A1 -A2-A3-C—A4)-ring system by a dotted bond.
R11 R11 R11 /N\ \N N—O O—N *--- \N/N"~ R11 R11 R11 R11 T2 T3 T4 T22 T23 R11 R11 R11 R11 R11 R11 T46 T47 where R11 is ndently defined as described herein. id="p-119" id="p-119" id="p-119" id="p-119" id="p-119" id="p-119"
[119] In a further particularly preferred embodiment, T is one of the 5-membered heteroaromatic s shown below, where the bond to the carbon atom of the (C—Bl—Bs) ring system is identified by a dotted bond marked with an asterisk, and the bond to the carbon atom of the (C-Al-Az-A3-C-A4)-ring system by a dotted bond.
\VC) 2015/0676" - 'if - PCT/EP20l4/O73795 R11 R11 11 N\ I? —O O—N R R11 \ \[\\j \ * - N/ * __ / *«\ u \ /\ \N,*' *' - \N/NT‘ R11 R11 R11 R11 T2 T3 T4 T22 T23 Where R11 is independently defined as described herein.
In an even more preferred embodiment, in the formula (I) and further general formulae detailed herein, A1 is C—R2 or N, ably C—RZ, A2 is CR3 or N, A3 is CR4, A4 is 0115 or N, 131 is CR6, B2 is C-H, B3 is CR8, B4 is C-H, B5 is CR10 or N, R1 is hydrogen, R2 is hydrogen, C1-C3-a1kyl, fluorine or chlorine, preferably H, R3 is hydrogen or halogen—substituted C1-C3-alkyl (preferably perfluorinated C1-C3-alkyl (CF3, CZFS or CsF7)), R4 is en, chlorine, fluorine, C1-C3-alkyl (such as -CH3), cyclopropyl, C1-C3-alkoxy (such as ), N—Cl-C4-alkylamino (-NH-Cl—Cg-alkyl such as -NH-CH3), C3-cycloalkylamino (such as —NH—C3H5), N-01—C3—alkoxy—01-C3-alkylamino (such as -NH-C2H4—O-CH3) or 1—pyrrolidiny1, more preferably chlorine, R5 is en or fluorine, ably H, R6 and R10 are each independently hydrogen, C1-C3-alky1 rably, R6 and R10 are each C1—C3-alkyl), Cl-Cg—alkoxy, halogen—substituted C1-C3-alkyl (preferably perfluorinated C1-C3-alkyl (CF3, C2F5 or C3F7)), halogen-substituted C1-C3-alkoxy (preferably perfluorinated C1—C3—alkoxy (OCF3, OC2F5 or OC3F7)), C1—C3-alkylsulphanyl, C1-C3—alkylsulphinyl, alkylsulphonyl, fluorine, bromine or chlorine (preferably, R6 and R10 are each chlorine), \K’O 2015/067647 - (J) [; PCT/EPZO 14/0737") (1‘lI R8 is halogen—substituted C1—C3-alkyl (preferably perfluorinated C1-C3—alkyl (C133, C2135 or C3F7)) or halogen-substituted C1-C3—alkoxy (preferably perfluorinated C1—C3-alkoxy (OCF3, OC2F5 or OCstl), R11 is en, cyano (CN) or amino (NHZ), is oxygen or sulphur, preferably oxygen, is alkyl, cyclopropyl, 1-(cyano)cyclopropyl, l-(perfluorinated C1-C3-a1kyl)cyclopropyl (such as (1-(trifluoromethyl)cyclopropyl), 1-(C1-C4-alkyl)cyclopropyl (such as 1-(tert- buty1)cyclopropyl), l-(thiocarbamoy1)cyclopropyl, halogen-substituted alkyl (e.g. CH2CF3, CH2CH2CF3), thietanyl, N-methylpyrazol-3 -yl, 2-oxo-2(2,2,2-trifluoroethylamino)ethyl, and is a T selected from the group consisting of T1 to T47, preferably T2, T3, T4, T22 or T23 (more ably T22 or T23).
In a further even more preferred embodiment, in the a (I) and further general formulae detailed herein, A1 is C-R2 or N, preferably C—RZ, A2 is CR3 or N, A3 is CR4, is 0115 or N, is CR6, is OH, is CR8, is C-H, is CR10 or N, is C1-C2-alkyl (methyl or ethyl, more preferably methyl), is hydrogen, C1-C3-alkyl, e or chlorine, preferably H, is hydrogen or halogen-substituted C1-C3-alkyl (preferably perfluorinated C1-C3—alky1 (CF3, C2F5 01‘ C3F7)), is en, chlorine, fluorine, C1-C3-a1ky1 (such as —CH3), cyclopropyl, C1—C3-alkoxy (such as -O-CH3), N—Cl—C4-alkylamino (-NH-C1—C3—alkyl such as —NH—CH3), C3-cycloalkylamino (such as —NH—C3H5), 3-alkoxy—C1-Cg-alkylamino (such as -NH-C2H4-O—CH3) or 1-pyrrolidiny1, more preferably chlorine, is hydrogen or fluorine, preferably H, "’0 67647 —_J) 'JI I R6 and R10 are each independently hydrogen, C1-C3-alkyl (preferably, R6 and R10 are each C1—C3—alkyl), C1-C3—alkoxy, halogen-substituted alkyl (preferably perfluorinated C1-C3-alkyl (CF3, C2F5 or C3F7)), halogen-substituted C1-C3—alk0xy (preferably rinated C1—C3-alkoxy (OCF3, OC2F5 or OC3F7)), C1-C3—alkylsulphanyl, C1-C3—alkylsulphinyl, C1-C3-alkylsulphonyl, fluorine, bromine or chlorine rably, R6 and R10 are each chlorine), R8 is halogen-substituted C1-C3-alkyl (preferably perfluorinated C1-C3—alkyl (CF3, C2F5 or C3F7)) or halogen-substituted C1-C3-alkoxy (preferably perfluorinated C1-C3—alkoxy (OCF3, OC2F5 or OC3F7))3 R11 is hydrogen, cyano (ON) or amino (NHZ), W is oxygen or sulphur, preferably oxygen, Q is C1-C3-alkyl, cyclopropyl, l-(cyano)cyclopropy1, fluorinated C1-C3-alkyl)cyclopropyl (such as ifluoromethyl)cyclopropyl), l-(C1-C4-alkyl)cyclopropyl (such as 1-(tert— butyl)cyclopropyl), 1—(thiocarbamoyl)cyclopropyl, halogen-substituted C1-C3-alkyl (e.g. CH2CF3, CHZCH2CF3), nyl, N—methylpyrazol-3 -yl, 2-oxo-2(2,2,2-trifluoroethylamino)ethyl, and T is a T selected from the group consisting of T1 to T47, preferably T2, T3, T4, T22 or T23 (more preferably T22 or T23).
A further preferred embodiment additionally relates to compounds of the formula (Ia) 83/ 2 \ \31 B\\ )\ D 4\Bs Ds/ 2‘- i} P1 R1 1 a A1‘/ \ W AgA (la) R1/ \Q in which R1, R", Q, W, A1, A2, A3, A4, B1, B2, B3, B4 and B5 are each defined as described herein, where not more than one moiety selected from A1, A2, A3, A4 is N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; or where one or two moieties selected from A1, A2, A3, A4 may be N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; and Vx’O 2(115/067647 - 36 » PCT/EPZOM/U73795 D1 and D2 are each independently C—R11 or a heteroatom, preferably C-R11 or a heteroatom ed from N, O and S, more preferably OR" or a atom selected from N and O; the D3 and D4 moieties are each ndently C or a heteroatom selected from N; where one (1) or two moieties selected from D1, D2, D3 and D4 are a heteroatom; is an aromatic system.
A further preferred embodiment onally relates to compounds of the formula (Ia') R /BZ\B1 A1‘/ A \4 W ARA (13') R1/ Q in which R1, R", Q, W, A1, A2, A3, A4, B1, B2, B4 and B5 are each defined as described herein, where not more than one moiety selected from A1, A2, A3, A4 is N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; or where one or two moieties selected from A1, A2, A3, A4 may be N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; D1 and D2 are each ndently C—R11 or a heteroatom, preferably C-R11 or a atom selected from N, O and S, more preferably C-R11 or a heteroatom selected from N and O; the D3 and D4 moieties are each independently C or a heteroatom selected from N; where one (1) or two moieties selected from D1, D2, D3 and D4 are a heteroatom; in other words, Where not more than one (1) or two moieties selected from D1, D2, D3 and D4 is/are a heteroatom, where one (1) or two moieties selected from D1, D2, D3 and D4 is a heteroatom selected from N and O in the case of D1 and D2, or N in the case of D3 and D4; is an aromatic system and R8 is as defined herein, preferably perfluorinated C1-C4-alkyl. id="p-124" id="p-124" id="p-124" id="p-124" id="p-124" id="p-124"
[124] A further preferred embodiment relates to compounds of the formula (Ib) V\’O 20157067647 — U.) \J — in WhiCh R15 R2, R4: R5: R5: R75 R83 R93 R103 R115 A2, Q5 D1: D2: D3 D4 and are eaCh defined as described herein, and where one (1) or two moieties selected from D1, D2, D3 and D4 are a heteroatom.
Two particularly preferred embodiments relate to compounds of the formula (Ib) and (Id) in which D1 is N, D2 is O and D3 and D4 are C; or D1 is C—R", D2 is N and D3 is N and D4 is C, Where R13 is H, halogen, cyano, nitro, amino or an optionally substituted C1—C6-alkyl, C1-C6-alkyloxy, C1-C6- alkylcarbonyl, C1-C6—alky1sulphanyl, C1-C6-alkylsulphinyl, C1-C6-alkylsulphonyl, preferably H or halogen such as F, Cl, Br or I, and more preferably H; and R1 is preferably H or R1 is preferably .
A r ularly preferred embodiment relates to compounds of the formula (Ib) and (Id) in which D1 is 0, D2 is N and D3 and D4 are C; Where R13 is H, halogen, cyano, nitro, amino or an optionally tuted C1-C6-alkyl, C1-C6-alkyloxy, alkylcarbonyl, C1—C6-alkylsulphanyl, C1-C6- alkylsulphinyl, C1-C6-alkylsulphony1, preferably H or halogen such as F, Cl, Br or I, and more preferably H; and R1 is preferably H or R1 is preferably methyl.
A further preferred embodiment relates to compounds of the formula (10) R R 8 / 6 R9 /IE1 D6 1,. D5 R10 D’ R 11 R 2 / \ O R4 R1/N\Q (10) "’0 2015/067647 - UJ CO | PCT/E17201 4/073795 in which R1, R2, R4, R5, R6, R7, R3, R9, R10, R11, A2 and Q are each defined as described herein and is an aromatic ; and and D6 is N a moiety ed from D4 and D6 is N, where the respective other moiety selected from D4 or C; and D5 is N or C—R"; under the condition that not more than two moieties selected from D4, D5 and D6 are N.
Preferred embodiments relate to compounds of the formula (10) in which D4 is N and D5 and D6 and D6 are each C—R"; in which D5 is N and D5 and D4 are each C-R"; or in which D4 and D5 are each N is OR". id="p-129" id="p-129" id="p-129" id="p-129" id="p-129" id="p-129"
[129] A further preferred embodiment relates to compounds of the formula (Id) B// 2a [31 33‘ )\ D 4§85 Os/. 2- 3; :;;/D1 R11 3\ A/ A 4 A1‘ MW§ 2 A3 RV \Q (Id) whereR1,R", Q, w, A1,A2, A3, A4,B1,B2, Bg, B4andB5, D1,D2, D3 andD4 and C):- are each defined as described herein, where not more than one (1) or two moieties selected from D1, D2, D3 and D4 are a heteroatom and where not more than one moiety selected from A1, A2, A3, A4 is N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N.
A particularly preferred embodiment relates to compounds of the formula (Ia), (Ib), (10) or (Id) in which R8 is C1-C6-alkyl, halogen-substituted C1-C6-alky1, C3-C6—cycloalkyl, halogen—substituted C3- Cé—cycloalkyl, C1-C6—alkoxy, halogen—substituted C1-C6-alkoxy, N—alkoxyiminoalkyl, halogen— substituted alkylsulphanyl, halogen—substituted C1—C6-alkylsulphinyl, halogen-substituted Cl-C6~ alkylsulphonyl, N—Cl-CG—alkylamino, MN—di-Cl-C4—alkylamino, and is n, cyano or nitro.
Examples are fluorine, chlorine, bromine, iodine, cyano, nitro, , ethyl, difluoromethyl, trichloromethyl, chlorodifluoromethyl, dichlorofluoromethyl, trifluoromethyl, chloromethyl, bromomethyl, l-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethy1, 2,2,2—trifluoroethyl, 1,2,2,2— tetrafluoroethyl, l-chloro—l,2,2,2-tetrafluoroethyl, 2,2,2-trichloroethyl, 2-chloro—2,2-difluoroethyl, 1,1- difluoroethyl, pentafluoroethyl, pentafluoro—tert-butyl, heptafluoro-n-propyl, heptafluoroisopropyl, oro—n—butyl, oro—sec—butyl, ropyl, cyclobutyl, y, ethoxy, n—propoxy, l— "7O 2015/067647 - 39 — methylethoxy, fluoromethoxy, difluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy, trifluoromethoxy, 2,2,2—trifluoroethoxy, 2—chloro-2,2-difluoroethoxy, pentafluoroethoxy, N- methoxyiminomethyl, l—(N-methoxyimino)ethyl, methylsulphanyl, methylsulphonyl, methylsulphinyl, trifluoromethylsulphonyl, trifluoromethylsulphinyl, trifluoromethylsulphanyl, MN—dimethylamino.
More preferably, R8 is halogen-substituted C1-C4-a1ky1 such as difluoromethyl, trichloromethyl, chlorodifluoromethyl, dichlorofluoromethyl, trifluoromethyl, l-fluoroethyl, 2-fluoroethyl, 2,2- difluoroethyl, 2,2,2-trifluor0ethyl, 2-tetraflu0roethyl, l-chloro-l,2,2,2-tetrafluoroethy1, 2,2,2- trichloroethyl, 2-chloro-2,2-difluoroethyl, 1,1-difluoroethyl, pentafluoroethyl, pentafluoro-tert-butyl, heptafluoro-n-propyl, heptafluoroisopropyl, nonafluoro—n-butyl, nonafluoro-sec-butyl; halogen- substituted C1-C4-alkoxy such as ethoxy, difluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2,2-difluoroethoxy, pentafluoroethoxy; trifluoromethylsulphonyl; trifluoromethylsulphinyl; or trifluoromethylsulphanyl.
Even more preferably, R8 is difluoromethyl, trichloromethyl, chlorodifluoromethyl, dichlorofluoromethyl, trifluoromethyl, l-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethy1, 2,2,2- trifluoroethyl, 2-tetrafluoroethyl, 1-chloro-1,2,2,2-tetrafluoroethy1, 2,2,2-trichloroethyl, ro- 2,2-difluoroethyl, 1,1-difluoroethyl, pentafluoroethyl, pentafluoro-tert-butyl, heptafluoro-n-propyl, heptafluoroisopropyl, nonafluoro-n-butyl, nonafluoro-sec-butyl, fluoromethoxy, difluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2,2- difluoroethoxy, pentafluoroethoxy, trifluoromethylsulphonyl, trifluoromethylsulphinyl or trifluoromethylsulphanyl. More preferably, R8 in compounds of the formula (1b) is perfluorinated C1-C3- alkyl such as perfluorinated propyl (-C3F7), perfluorinated ethyl (C2135) or rinated methyl (CF3), most ably perfluorinated propyl ) or perfluorinated methyl.
Particularly preferred compounds corresponding to the compounds of the formula (Ia) are compounds of the formula (I-T2), , (I—T4), (I-T22) and (I—T23). id="p-133" id="p-133" id="p-133" id="p-133" id="p-133" id="p-133"
[133] One embodiment of the present invention relates to compounds of the formula (I—T2) and (I-T4).
A further ment s to compounds of the formula (I-T3).
A further embodiment relates to compounds of the formulae (I—T22) and (I—T23).
Therefore, a very ularly preferred embodiment relates to compounds of the a (I-T2).
A preferred ment relates in turn to compounds of the formula (I-T2) in which R1 is H. A further preferred embodiment relates in turn to nds of the formula (I-T2) in which R1 is methyl.
A further very particularly preferred embodiment relates to compounds of the a (I-T3). A preferred embodiment relates in turn to nds of the formula (I-T3) in which R1 is H. A further preferred embodiment relates in turn to compounds of the formula (I-T3) in which R1 is methyl.
‘WO 67647 - 4O — A further very particularly preferred embodiment relates to compounds of the formula . A preferred embodiment relates in turn to compounds of the formula (I—T4) in which R1 is H. A further red embodiment relates in turn to compounds of the formula (I-T4) in which R1 is methyl.
A fiarther very particularly preferred embodiment relates to compounds of the formula (I-T22).
A preferred ment relates in turn to compounds of the formula (I—T22) in which R1 is H. A r preferred embodiment relates in turn to compounds of the formula (I—T22) in which R1 is methyl.
A further very particularly red embodiment relates to compounds of the formula (I-T23).
A preferred embodiment s in turn to compounds of the formula (I-T23) in which R1 is H. A further preferred embodiment relates in turn to compounds of the formula (I-T23) in which R1 is methyl. /82\ 11 / B1 R B R11 4%85 \ A4 W A‘\><\ A2’:Aa N‘—Q (I-T2) in which R1, A1, A2, A3, A4, R", B1, B2, B4, B5, R8, R", Q and W are each defined as described herein, where not more than one moiety selected from A1, A2, A3, A4 is N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; or where one or two moieties selected from A1, A2, A3, A4 may be N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; or in which "’0 2015/067647 — 4] — ZOl4/G7379S R1, A1, A2, A3, A4, R11, B1, B2, B4, B5, R8, R", Q and W are each defined as described herein, where not more than one moiety ed from A1, A2, A3, A4 is N and not more than one moiety selected from B], B2, B3, B4 and B5 is N; or where one or two moieties selected from A1, A2, A3, A4 may be N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; or (I—T4) in which R1, A1, A2, A3, A4, R", B1, B2, B4, B5, R8, R", Q and W are each defined as described herein, where not more than one moiety selected from A1, A2, A3, A4 is N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; or where one or two moieties selected from A1, A2, A3, A4 may be N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; or (T-22) in which R1, A1, A2, A3, A4, R", B1, B2, B4, B5, R8, R", Q and W are each defined as described herein, where not more than one moiety selected from A1, A2, A3, A4 is N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; or where one or two moieties selected from A1, A2, A3, A4 may be N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; or ‘ — 42 — PCT/EPZOl4—/O7379S (I—T23) in which R1, A1, A2, A3, A4, R", B, B2, B4, B5, R8, R", Q and W are each defined as described herein, where not more than one moiety ed from A1, A2, A3, A4 is N and not more than one moiety ed from B1, B2, B3, B4 and B5 is N; or Where one or two moieties selected from A1, A2, A3, A4 may be N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N.
A further preferred embodiment relates to compounds of the formula (In) (T = T2) / '81 R11 R B5 \\ R" N‘N 5 R4 N‘R1 Q (In) in which R1, Q, W, A2, B1, B5, R2, R4, R5, R6, R7, R8, R9 and R11 are each defined as described herein, in which R1 represents H or in which R1 represents methyl.
A further-preferred embodiment relates to compounds of the formula (In) in which W is O; Q is ally substituted a1ky1 or optionally substituted cycloa1kyl or an unsaturated 4-, 5- or 6-membered heterocyclic ring optionally substituted by one, two or three V substituents, where V is independently halogen, cyano, nitro, oxo (=0), optionally halogen-substituted C1-C6—a1ky1, C1—C4-alkenyl, C1—C6—alkoxy, C1-C6- alkylsulphanyl, C1—C6—alkylsulphiny1, alky1sulphony1; preferably halogen-substituted C1—C3-alkyl; with cyano, hydroxyl or carbonamide (—C(=O)N(R)2 where R is independently H or C1—C3—a1ky1, substituted C1-C3—alkyl; C3- cycloalkyl; cyano-substituted, halogen—substituted, nitro-substituted or halogenated C1— \V0 ZOE/067647 - 43 — PCT/EPZOl4/O7379S Cz—alkyl-substituted C3—cycloalkyl; an unsaturated 4-, 5- or 6—me1nbered heterocyclic ring optionally substituted by one, two or three V and containing one or two heteroatoms ed from a group consisting of N, O and S, where V is independently halogen, cyano, nitro, 0x0 (=0), optionally halogen—substituted C1—Cé-alkyl; more ably fluorinated C1-C3-alky1 such as CF3, CH2CF3 or CH2CH2CF3; C1-C3- alkyl substituted by carbonamide (—C(=O)N(R)2 where R is independently H, C1—C3— alkyl or halogen-substituted C1-C3—alkyl), such as 2-oxo(2,2,2- trifluoroethylamino)ethyl; cyclopropyl; cyano-substituted or fluorinated C1-C2-alkyl— substituted cyclopropyl such as 1-(cyano)cyclopropyl or 1- (trifluoromethyl)cyclopropyl); a 4-membered heterocyclic ring containing one heteroatom selected from a group consisting ofN, O and S, such as thietan-3 -yl; R7 and R9 are each H; in each case is H; is H; is H, halogen or C1-C4-alkyl, preferably H, fluorine, chlorine or methyl; is H or halogen, preferably H, fluoro or chloro; is H or halogen, preferably H, fluoro or chloro; is N or C-Rlo, preferably C—R10 in which is hydrogen, C1-C3—alky1, C1—C3-alkoxy, halogen-substituted C1-C3-alkyl (preferably perfluorinated C1-C3—alky1 (CF3, C2135 or C3F7)), halogen-substituted Cl-C3—alkoxy (preferably perfluorinated C1—C3-alkoxy (OCF3, OC2F5 or OC3F7)), C1—C3- alkylsulphanyl, C1-C3-alkylsulphinyl, alkylsulphonyl, fluorine, e or chlorine; is N or C-R3, preferably C-R3 in which is H, halogen, or ally substituted C1—C4-alkyl, preferably H, e, chlorine or optionally halogen-substituted C1—C2-alkyl, more preferably H or fluoro-substituted methyl, for example perfluoromethyl; is en, C1-C3-alkyl, C1-C3-alkoxy, halogen-substituted C1—C3—alkyl (preferably perfluorinated C1-C3-alkyl (CF3, C2F5 or C3F7)), halogen-substituted C1-C3-alkoxy rably perfluorinated C1—C3—alkoxy (OCF3, OC2F5 or OC3F7)), C1-C3- ulphanyl, C1—C3-alkylsulphinyl, C1-C3—alkylsulphonyl, fluorine, chlorine or bromine, preferably e, chlorine, bromine, C1-C2-alkyl, halogen-substituted C1-C2- alkyl (e.g. romethyl) or optionally halogen-substituted C1-C2—alkoxy, more preferably fluorine, e, chlorine, methyl, ethyl, fluorinated methyl or fluorinated ethyl (more preferably perfluoromethyl or perfluoroethyl), fluorinated methoxy or fluorinated ethoxy (more ably perfluoromethoxy); is halogen or ally halogen-substituted C1-C4-alkyl or optionally halogen- substituted C1-C4—alkoxy, preferably n—substituted C1—C3—alkyl or halogen— "’0 ZOE/067647 - 4—"; — PCT/EPZOl4/073795 substituted C1-C3-alkoxy, more preferably n—substituted C1—C3—alkyl such as ated C1—C3-alkyl (e.g. fluorinated C3-alkyl such as perfluoropropyl).
A further-preferred embodiment s to compounds of the formula (In) in which w is O; Q is optionally substituted Cl-C4—a1ky1 or optionally substituted C3-Cé—cycloalkyl or an unsaturated 4-, 5- or 6-membered cyclic ring optionally substituted by one, two or three V substituents, where V is independently halogen, cyano, nitro, oxo (=0), optionally n—substituted C1-C6-a1kyl, C1-C4-a1kenyl, C1—C6-alkoxy, C1-C6- ulphanyl, C1—C6—alkylsulphinyl, C1-C6-alkylsulphonyl; ably halogen-substituted C1-C3—alky1; with cyano, hydroxyl or carbonamide (—C(=O)N(R)2 where R is independently H or C1-C3—alky1, substituted C1-C3-alkyl; C3- cycloalkyl; cyano-substituted, halogen-substituted, substituted or halogenated C1- Cz-alkyl-substituted C3-cycloa1ky1; an unsaturated 4-, 5— or ered heterocyclic ring optionally substituted by one, two or three V and containing one or two heteroatoms selected from a group consisting of N, O and S, where V is independently halogen, cyano, nitro, oxo (=0), optionally halogen—substituted C1-C6-alky1; more preferably fluorinated C1-C3-alkyl such as CF3, CH2CF3 or CH2CH2CF3; C1-C3- alkyl substituted by carbonamide (—C(=O)N(R)2 where R is independently H, C1-C3- alkyl or halogen-substituted C1-C3—alkyl), such as 2—oxo—2-(2,2,2- trifluoroethylamino)ethyl; cyclopropyl; cyano—substituted or fluorinated C1—C2-alkyl- substituted cyclopropyl such as 1-(cyano)cyclopropy1 or 1- (trifluoromethyl)cyclopropyl); a 4-membered heterocyclic ring containing one heteroatom selected from a group consisting of N, O and S, such as n—3 -y1; R7 and R9 are each H; in each case is H; is methyl; is H, halogen or alky1, preferably H, fluorine, chlorine or methyl; is H or halogen, ably H, fluoro or ; is H or halogen, preferably H, fluoro or chloro; is N or C-Rlo, preferably OR" in which is hydrogen, C1-C3-alkyl, C1-C3—alkoxy, halogen-substituted C1-C3-alkyl (preferably perfluorinated C1-C3-alkyl (CF3, C2F5 or C3F7)), halogen-substituted C1-C3-alkoxy (preferably perfluorinated C1-C3-alkoxy (OCFg, OC2F5 or OC3F7)), C1—C3- alkylsulphanyl, C1—C3-a1kylsulphinyl, C1-C3-alkylsulphonyl, fluorine, bromine or chlorine; is N or C—R3, preferably C-R3 in which 'WO 67647 — 45 — Zfll4/O7379S R3 is H, halogen, or optionally tuted C1—C4—alkyl, preferably H, fluorine, chlorine or optionally halogen-substituted C1-C2-alkyl, more preferably H or fluoro—substituted methyl, for example perfluoromethyl; R6 is hydrogen, C1-C3-alkyl, C1—C3—alkoxy, halogen-substituted C1-C3—alkyl (preferably perfluorinated C1-C3-alkyl (CF3, C2F5 or C3F7)), halogen—substituted alkoxy rably perfluorinated C1-C3—alkoxy (OCF3, OC2F5 or OC3F7)), C1-C3- alkylsulphanyl, C1-C3-alkylsulphinyl, C1-C3-alkylsulphonyl, fluorine, chlorine or bromine, preferably fluorine, ne, bromine, C1-C2-alkyl, halogen-substituted C1-C2- alkyl (e.g. perfluoromethyl) or optionally halogen-substituted C1-C2—alkoxy, more l 0 preferably fluorine, bromine, chlorine, methyl, ethyl, fluorinated methyl or fluorinated ethyl (more preferably perfluoromethyl or roethyl), fluorinated methoxy or fluorinated ethoxy (more preferably perfluoromethoxy); R8 is halogen or optionally n—substituted alkyl or optionally halogen- substituted C1—C4-alkoxy, preferably halogen-substituted C1—C3-alky1 or halogen- 1 5 substituted C1-C3—alkoxy, more preferably halogen-substituted C1-C3-alkyl such as ated C1-C3-alkyl (e. g. fluorinated C3-alkyl such as perfluoropropyl). [1 44] A further red embodiment relates to compounds of the formula (16) (T = T3) (16) in which R1, Q, W, A2, B1, B5, R2, R4, R5, R6, R7, R8, R9 and R11 are each defined as described herein, in which R1 represents H or in which R1 represents methyl.
A further-preferred embodiment relates to compounds of the formula (1e) in which w is O; Q is optionally substituted C1-C4—alkyl or optionally substituted C3—C6-cycloalkyl or an unsaturated 4-, 5- or 6-membered heterocyclic ring optionally substituted by one, two or three V substituents, Where V is independently halogen, cyano, nitro, oxo (=0), optionally halogen-substituted C1-C6-alkyl, C1-C4—alkenyl, C1-C6-alkoxy, C1—C6— alkylsulphanyl, alkylsulphinyl, C1-C6—alkylsulphonyl; W70 2015/067647 PCT/EP2014-/073795 preferably n—substituted C1—C3—alkyl; with cyano, hydroxyl or carbonamide (-C(=O)N(R)2 where R is independently H or C1-C3—alkyl, substituted C1-C3-alkyl; C3- cycloalkyl; cyano-substituted, halogen-substituted, nitro-substituted or halogenated C1- Cz-alkyl-substituted C3-cycloalkyl; an unsaturated 4—, 5- or 6-membered heterocyclic ring optionally substituted by one, two or three V and containing one or two heteroatoms selected from a group consisting of N, O and S, where V is independently halogen, cyano, nitro, 0x0 (=0), optionally halogen-substituted C1-C6-alkyl; more preferably fluorinated C1-C3-alkyl such as CF3, CHZCFg} or CH2CH2CF3; C1-C3- alkyl substituted by carbonamide (—C(=O)N(R)2 where R is independently H, C1-C3- alkyl or halogen-substituted C1-C3-alkyl), such as 2—oxo-2—(2,2,2- trifluoroethylamino)ethyl; cyclopropyl; cyano-substituted or fluorinated alkyl- substituted cyclopropyl such as l-(cyano)cyclopropyl or 1- (trifluoromethyl)cyclopropyl); a 4-membered heterocyclic ring containing one atom selected from a group consisting of N, O and S, such as n—3—yl; are each H; in each case is H; is H; is H, halogen or C1-C4—alkyl, preferably H, e, chlorine or methyl; is H or halogen, preferably H, fluoro or chloro; is H or n, preferably H, fluoro or chloro; is N or C-Rlo, preferably C—R10 in which is hydrogen, C1—C3-alkyl, C1—C3-alkoxy, halogen-substituted C1—C3—alkyl (preferably perfluorinated C1—C3-alkyl (CF3, C2F5 or C3F7)), halogen—substituted C1~C3-alkoxy (preferably perfluorinated C1-C3—alkoxy (OCF3, OC2F5 or OC3F7)), C1-C3— alkylsulphanyl, C1-C3-alkylsulphinyl, C1—C3-alkylsulphonyl, fluorine, bromine or chlorine; is N or C-RS, preferably C-R3 in which is H, halogen, or optionally substituted C1—C4-alkyl, preferably H, e, chlorine or optionally halogen-substituted C1—C2-alkyl, more preferably H or fluoro-substituted methyl, for example perfluoromethyl; is hydrogen, C1-C3-alkyl, alkoxy, n-substituted C1-C3—alkyl (preferably perfluorinated C1—C3-alkyl (CF3, C2F5 or C3F7)), halogen-substituted C1-C3-alkoxy (preferably perfluorinated C1-C3-alkoxy (OCF3, OC2F5 or OC3F7)), C1-C3— alkylsulphanyl, C1-C3-alkylsulphinyl, C1-C3—alkylsulphonyl, e, chlorine or bromine, preferably fluorine, chlorine, bromine, C1—C2-alkyl, n-substituted C1-C2- alkyl (e.g. perfluoromethyl) or optionally halogen—substituted alkoxy, more preferably fluorine, bromine, chlorine, , ethyl, fluorinated methyl or fluorinated \VC) MUS/067647 - 47 — ethyl (more preferably perfluoromethyl or perfluoroethyl), fluorinated methoxy or fluorinated ethoxy (more ably perfluoromethoxy); is halogen or optionally halogen-substituted C1-C4-alkyl or optionally halogen- substituted C1-C4-alkoxy, preferably halogen-substituted C1-C3-alkyl or halogen- substituted alkoxy, more preferably halogen—substituted Cl—C3—alkyl such as fluorinated C1—C3-alkyl (e. g. fluorinated C3-alkyl such as perfluoropropyl).
A further-preferred embodiment s to compounds of the a (Ie) in which W is O; Q is optionally substituted C1—C4-alkyl or optionally substituted C3-C6-cycloalkyl or an unsaturated 4-, 5- or ered heterocyclic ring optionally substituted by one, two or three V substituents, where V is independently halogen, cyano, nitro, oxo (=0), optionally halogen—substituted C1-C6-alkyl, alkenyl, C1-C6—alkoxy, C1-C5- ulphanyl, C1-C6—alkylsulphinyl, C1-C6-alkylsulphonyl; preferably halogen-substituted C1-C3-alkyl; with cyano, hydroxyl or carbonamide (—C(=O)N(R)2 where R is independently H or C1—C3-alkyl, substituted C1-C3—alkyl; C3- cycloalkyl; cyano—substituted, n-substituted, nitro-substituted or halogenated C1- Cz-alkyl-substituted C3-cycloalkyl; an unsaturated 4-, 5- or 6-membered heterocyclic ring ally substituted by one, two or three V and containing one or two heteroatoms selected from a group consisting of N, O and S, where V is independently halogen, cyano, nitro, oxo (=0), optionally halogen-substituted C1-C6—alkyl; more preferably fluorinated C1-C3-alkyl such as CF3, CH2CF3 or CHZCHZCF3; C1—C3- alkyl substituted by amide (—C(=O)N(R)2 where R is independently H, C1-C3- alkyl or halogen—substituted C1-C3-alkyl), such as 2-oxo—2-(2,2,2- trifluoroethylamino)ethyl; cyclopropyl; cyano—substituted or fluorinated C1—C2-alkyl— substituted cyclopropyl such as 1-(cyano)cyclopropyl or 1- (trifluoromethyl)cyclopropyl); a 4-membered heterocyclic ring containing one heteroatom selected from a group consisting of N, O and S, such as thietan-3 —yl; R7 and R9 are each H; in each case is H; is methyl; is H, halogen or Cl-C4-alkyl, preferably H, fluorine, chlorine or ; is H or n, preferably H, fluoro or ; is H or halogen, preferably H, fluoro or chloro; is N or C-Rm, preferably C-R10 in which is hydrogen, C1-C3-alkyl, C1—C3-alkoxy, halogen-substituted C1-C3-alkyl (preferably perfluorinated C1—C3-alkyl (CFg, CZFS or C3F7)), halogen-substituted C1—C3—alkoxy W0 EMS/067647 — 48 — PCT/EP2014-/073795 (preferably perfluorinated C1—C3—alkoxy (OCF3, OC2F5 or OC3F7)), C1—C3- alkylsulphanyl, C1—C3-alkylsulphinyl, C1-C3—alkylsulphonyl, fluorine, bromine or chlorine; A2 is N or C-RS, preferably C-R3 in which R3 is H, halogen, or optionally substituted C1-C4-alkyl, preferably H, fluorine, chlorine or optionally halogen—substituted C1-C2-alkyl, more preferably H or fluoro—substituted methyl, for example perfluoromethyl; R6 is hydrogen, C1-C3—alkyl, C1-C3-alkoxy, halogen-substituted C1—C3-alkyl (preferably perfluorinated C1-C3-alkyl (CF3, C2135 or , halogen-substituted alkoxy (preferably perfluorinated C1-C3-alkoxy (OCFg, OC2F5 or OC3F7)), C1-C3- ulphanyl, C1-C3-alkylsulphinyl, Cl-Cg-alkylsulphonyl, fluorine, chlorine or bromine, preferably fluorine, chlorine, bromine, C1—C2-alkyl, halogen-substituted C1-C2- alkyl (e.g. perfluoromethyl) or optionally halogen-substituted C1-C2-alkoxy, more preferably fluorine, bromine, chlorine, methyl, ethyl, fluorinated methyl or ated ethyl (more preferably perfluoromethyl or perfluoroethyl), ated y or fluorinated ethoxy (more preferably perfluoromethoxy); R8 is halogen or optionally halogen-substituted C1—C4-alkyl or ally halogen— substituted alkoxy, preferably halogen-substituted alkyl or halogen- substituted C1—C3-alkoxy, more preferably n-substituted C1-C3-alkyl such as fluorinated C1-C3—alkyl (e.g. fluorinated Cg-alkyl such as perfluoropropyl).
A further-preferred embodiment relates to compounds of the a (If) (T = T23) (If) in which R1, Q, W, A2, B1, B5, R2, R4, R5, R6, R7, R8, R9 and R11 are each defined as described herein, in which R1 represents H or in which R1 represents methyl.
A preferred embodiment relates to compounds of the formula (If) in which W is O; \X’O 2015/067647 — 49 - PCT/EPZGl4/U7379S is optionally substituted C1—C4-alkyl or optionally substituted C3-C6-cycloalkyl or an unsaturated 4-, 5— or 6—me1nbered heterocyclic ring Optionally tuted by one, two or three V substituents, where V is independently halogen, cyano, nitro, oxo (=0), optionally halogen-substituted C1-C5-alkyl, alkenyl, alkoxy, C1-C6- alkylsulphanyl, C1-C6-alkylsulphinyl, C1-C6-alkylsulphonyl; preferably halogen-substituted C1—C3-alkyl; with cyano, hydroxyl or carbonamide (-C(=O)N(R)2 where R is independently H or C1-C3-alkyl, substituted C1—C3-alkyl; C3- cycloalkyl; cyano-substituted, halogen-substituted, nitro-substituted or halogenated C1- Cz—alkyl-substituted C3-cycloa1kyl; an unsaturated 4-, 5- or 6-membered heterocyclic ring optionally substituted by one, two or three V and containing one or two heteroatoms selected from a group consisting of N, O and S, where V is independently halogen, cyano, nitro, oxo (=0), optionally halogen-substituted C1-C6—alkyl; more ably fluorinated C1-C3-alkyl such as CF3, CH2CF3 or CHZCH2CF3; C1-C3- alkyl substituted by carbonamide (—C(=O)N(R)2 where R is independently H, C1-C3- alkyl or halogen-substituted C1—C3-alkyl), such as 2-ox0(2,2,2- trifluoroethylamino)ethyl; cyclopropyl; cyano-substituted or ated C1-C2-alkyl- substituted cyclopropyl such as l-(cyano)cyclopropyl or 1— (trifluoromethyl)cyclopropyl); a 4-membered cyclic ring containing one heteroatom selected from a group consisting of N, O and S, such as n-3 -yl; R7 and R9 are each H; in each case is H; is H; is H, halogen or C1—C4-alkyl, preferably H, fluorine, chlorine or methyl; is H or halogen, preferably H, fluorine or chlorine; is H or halogen, preferably H, fluorine or ne; is N or C—RIO, preferably C-R10 in which is H, halogen, C1—C4-alkyl or C1-C4-alkoxy, preferably H, fluorine, bromine, chlorine, alkyl or C1-C2—alkoxy, more preferably H, chlorine, e, fluorine, methyl or methoxy; is N or C-R3, preferably OR3 in which is H, halogen, or optionally substituted C1-C4-alkyl, preferably H, fluorine, ne or ally halogen-substituted C1—C2—alkyl, more preferably H or fluorine-substituted methyl, for example perfluoromethyl; is H, halogen, optionally substituted C1—C4-alkyl or optionally substituted C1-C4-alkoxy, preferably e, chlorine, C1-C2-alkyl, halogen-substituted C1-C2—alkyl (e.g. perfluoromethyl) or ally halogen-substituted C1—C2-alkoxy, more preferably fluorine, bromine, chlorine, methyl, ethyl, fluorinated methyl or fluorinated ethyl (more ‘NO 67647 — 50 - PCT/EPZO 14/073795- preferably perfluoromethyl or perfluoroethyl), ated methoxy or fluorinated ethoxy (more preferably perfluoromethoxy); is halogen or ally halogen-substituted C1-C4-alkyl or optionally halogen— substituted C1—C4-alkoxy, preferably halogen-substituted C1-C3-alkyl or halogen- substituted C1-C3-alkoxy, more preferably halogen-substituted C1-C3-alkyl such as fluorinated C1-C3-alkyl (e. g. fluorinated C3-alkyl such as perfluoropropyl).
A preferred embodiment relates to compounds of the formula (If) in which W is O; Q is optionally substituted C1-C4-alkyl or optionally substituted C3-C6-cycloalkyl or an unsaturated 4-, 5— or 6-membered cyclic ring optionally substituted by one, two or three V substituents, where V is independently halogen, cyano, nitro, oxo (=0), optionally halogen-substituted C1—C6-alkyl, C1-C4-alkenyl, C1-C6-alkoxy, C1—C6- alkylsulphanyl, C1—C5-alkylsulphinyl, C1-Cé-alkylsulphonyl; preferably n-substituted C1-C3-alkyl; with cyano, hydroxyl or carbonamide (-C(=O)N(R)2 where R is independently H or C1-C3—alkyl, substituted C1—C3-alkyl; C3- cycloalkyl; cyano-substituted, halogen-substituted, nitro-substituted or halogenated C1- Cz-alkyl-substituted Cg-cycloalkyl; an rated 4-, 5- or 6-membered heterocyclic ring optionally substituted by one, two or three V and containing one or two heteroatoms selected from a group consisting of N, O and S, where V is independently halogen, cyano, nitro, oxo (=0), optionally halogen-substituted a1kyl; more preferably ated C1—C3—alkyl such as CF3, CH2CF3 or CHZCHZCF3; C1—C3- alkyl substituted by carbonamide (—C(=O)N(R)2 where R is independently H, C1-C3— alkyl or halogen-substituted C1-C3-alkyl), such as 2—oxo(2,2,2- trifluoroethylamino)ethyl; cyclopropyl; cyano-substituted or fluorinated C1-C2-alkyl- substituted cyclopropyl such as 1 -(cyano)cyclopropyl or 1 - (trifluoromethyl)cyclopropyl); a 4-membered heterocyclic ring containing one heteroatom ed from a group consisting of N, O and S, such as thietan—3 -y1; R7 and R9 are each H; in each case is H; is methyl; is H, n or C1-C4—alky1, preferably H, fluorine, chlorine or methyl; is H or halogen, ably H, fluorine or chlorine; is H or halogen, preferably H, fluorine or ne; is N or C-Rlo, preferably C-R10 in which is hydrogen, C1—C3—alkyl, C1-C3—alkoxy, halogen-substituted C1-C3-alkyl (preferably perfluorinated C1-C3-alkyl (CF3, C2F5 or C3F7)), halogen-substituted alkoxy (preferably perfluorinated C1-C3—a1koxy (OCF3, OC2F5 or OC3F7)), C1-C3- "’0 20154067647 — (,1‘ ,_r l PCT/EPZGM/O7379S alkylsulphanyl, C1—C3-alkylsulphinyl, C1—C3-alkylsulphonyl, fluorine, bromine or chlorine; A2 is N or C-Ra, preferably OR3 in which R3 is H, halogen, or optionally substituted C1-C4-alkyl, preferably H, fluorine, chlorine or optionally halogen-substituted C1-C2-alkyl, more preferably H or fluoro-substituted methyl, for example perfluoromethyl; R6 is hydrogen, C1-C3-alkyl, C1—C3-alkoxy, halogen-substituted C1-C3-a1ky1 (preferably perfluorinated C1-C3-alkyl (CF3, C2F5 or C3F7)), halogen—substituted C1-C3—alkoxy (preferably rinated C1-C3-alkoxy (OCF3, OC2F5 or OC3F7)), C1-C3- alkylsulphanyl, C1-C3-alkylsulphinyl, C1—C3-alkylsulphonyl, fluorine, chlorine or bromine, preferably fluorine, chlorine, bromine, C1-C2-alkyl, halogen-substituted C1-C2- alkyl (e.g. perfluoromethyl) or ally halogen-substituted alkoxy, more preferably fluorine, e, chlorine, methyl, ethyl, ated methyl or fluorinated ethyl (more preferably perfluoromethyl or perfluoroethyl), fluorinated methoxy or fluorinated ethoxy (more preferably perfluoromethoxy); R8 is halogen or optionally n-substituted C1—C4-alkyl or optionally n- substituted C1-C4—alkoxy, preferably halogen-substituted C1-C3-alkyl or halogen— substituted C1-C3-alkoxy, more preferably halogen-substituted C1-C3—alkyl such as fluorinated C1-C3-alky1 (e. g. fluorinated Cg-alkyl such as perfluoropropyl). id="p-150" id="p-150" id="p-150" id="p-150" id="p-150" id="p-150"
[150] A further-preferred embodiment s to compounds of the formula (Ig) (T = T4) (Ig) in which R1, Q, W, A2, B1, B5, R2, R4, R5, R6, R7, R8, R9 and R11 are each defined as described herein, in which R1 represents H or in which R1 represents methyl. id="p-151" id="p-151" id="p-151" id="p-151" id="p-151" id="p-151"
[151] A preferred embodiment s to compounds of the formula (Ig) in which W is O; "’0 2015/067647 5: PCT/EPZ(ll4-/07379S is optionally substituted C1-C4-alkyl or optionally substituted C3—C6—cycloalkyl or an unsaturated 4—, 5— or 6-membered cyclic ring optionally substituted by one, two or three V substituents, where V is independently halogen, cyano, nitro, oxo (=0), optionally halogen-substituted C1—C6-alkyl, C1—C4-alkenyl, C1-C6—alkoxy, C1—Cé- ulphanyl, C1-C6-alkylsulphiny1, C1-C6-alky1sulphonyl; preferably halogen-substituted C1-C3-alkyl; with cyano, hydroxyl or amide (—C(=O)N(R)2 where R is independently H or C1-C3-alkyl, substituted C1-C3—a1kyl; C3- cycloalkyl; substituted, halogen-substituted, nitro-substituted or halogenated C1- Cz-alkyl-substituted Cg-cycloalkyl; an unsaturated 4—, 5- or ered heterocyclic ring optionally substituted by one, two or three V and containing one or two heteroatoms selected from a group consisting of N, O and S, where V is ndently halogen, cyano, nitro, oxo (=0), optionally halogen-substituted C1-C6—alky1; more preferably fluorinated C1-C3-alkyl such as CF3, CHZCF3 or CchHZCF3; C1-C3- alkyl substituted by carbonamide (—C(=O)N(R)2 where R is independently H, C1-C3- alkyl or halogen-substituted C1-C3-alkyl), such as 2-0X0(2,2,2- trifluoroethylamino)ethy1; cyclopropyl; cyano—substituted or fluorinated C1-C2-alkyl- substituted cyclopropyl such as l -(cyano)cyclopropyl or 1 - (trifluoromethyl)cyclopropyl); a 4-membered heterocyclic ring containing one heteroatom selected from a group consisting of N, O and S, such as thietan-3 -yl; are each H; in each case is H; is H; is H, halogen or C1—C4-alkyl, preferably H, fluorine, chlorine or methyl; is H or halogen, preferably H, fluorine or chlorine; is H or halogen, preferably H, fluorine or chlorine; is N or C-Rlo, preferably C-R10 in which is hydrogen, C1—C3—alkyl, C1-C3—alkoxy, halogen-substituted C1-C3-alky1 rably perfluorinated C1-C3—alkyl (CF3, CZFS or C3F7)), halogen-substituted C1-C3-alkoxy rably perfluorinated C1—C3-alkoxy (OCF3, OC2F5 or OC3F7)), C1-C3— alkylsulphanyl, C1-C3-alkylsulphiny1, C1-C3—a1kylsulphonyl, e, bromine or chlorine; is N or C-R3, preferably C-R3 in which is H, n, or optionally substituted C1-C4-a1kyl, preferably H, fluorine, chlorine or optionally halogen-substituted C1-C2-alkyl, more preferably H or fluoro-substituted methyl, for example perfluoromethyl; is en, C1-C3—alkyl, C1-C3-alkoxy, halogen—substituted C1-C3-alkyl (preferably perfluorinated C1-C3-alkyl (CF3, C2135 or , halogen-substituted C1-C3—alkoxy (preferably rinated C1-C3—alkoxy (OCF3, OCZFS or OC3F7)), C1-C3- ‘W0 EMS/067647 — (J! D.) I P2014/G73795 alkylsulphanyl, C1-C3-alkylsulphinyl, C1-C3—alkylsulphonyl, fluorine, chlorine or bromine, preferably fluorine, chlorine, bromine, C1-C2-alkyl, halogen-substituted C1—C2- alkyl (e.g. perfluoromethyl) or optionally halogen-substituted alkoxy, more preferably fluorine, bromine, chlorine, methyl, ethyl, fluorinated methyl or fluorinated ethyl (more preferably perfluoromethyl or perfluoroethyl), fluorinated methoxy or ated ethoxy (more preferably perfluoromethoxy); is halogen or optionally halogen-substituted C1-C4-alky1 or optionally n— substituted C1-C4-alkoxy, preferably halogen-substituted alkyl or halogen— substituted alkoxy, more preferably halogen-substituted alky1 such as fluorinated C1-C3-alkyl (e. g. fluorinated C3-alkyl such as perfluoropropyl).
A preferred embodiment relates to compounds of the formula (1g) in which W is O; Q is optionally tuted C1-C4—alkyl or optionally substituted C3—C6-cycloalkyl or an unsaturated 4-, 5- or 6—membered heterocyclic ring optionally substituted by one, two or three V substituents, where V is ndently halogen, cyano, nitro, oxo (=0), optionally halogen-substituted C1-C6-alkyl, C1-C4-alkenyl, C1-C6-alkoxy, C1-C6- alkylsulphanyl, C1—C5-alkylsulphinyl, C1-C6-alkylsulphonyl; preferably halogen—substituted Cl-Cg-alkyl; with cyano, hydroxyl or carbonamide (-C(=O)N(R)2 where R is independently H or C1-C3—alky1, substituted C1-C3-alkyl; C3- cycloalkyl; cyano-substituted, halogen-substituted, nitro—substituted or halogenated C1- Cz—alkyl-substituted Cg-cycloalkyl; an unsaturated 4-, 5— or 6-membered heterocyclic ring optionally substituted by one, two or three V and containing one or two heteroatoms selected from a group consisting of N, O and S, where V is ndently halogen, cyano, nitro, oxo (=0), optionally halogen-substituted C1-C6-alkyl; more preferably fluorinated C1—C3—alkyl such as CF3, CHZCF3 or CHZCH2CF3; C1-C3- alkyl substituted by amide (—C(=O)N(R)2 where R is independently H, C1-C3- alkyl or halogen—substituted alkyl), such as 2—oxo-2—(2,2,2- trifluoroethylamino)ethyl; cyclopropyl; cyano-substituted or fluorinated C1—C2—alkyl- substituted cyclopropyl such as 1 -(cyano)cyclopropyl or 1 - (trifluoromethyl)cyclopropyl); a 4-membered heterocyclic ring containing one heteroatom selected from a group ting of N, O and S, such as thietan—3 -yl; R7 and R9 are each H; in each case is H; is methyl; is H, halogen or alkyl, preferably H, fluorine, chlorine or methyl; is H or halogen, preferably H, fluorine or chlorine; is H or halogen, preferably H, fluorine or chlorine; ' — 54 — PCT/EPZOI4/O7379S B5 is N or C-Rlo, preferably C-R10 in which R10 is hydrogen, C1-C3-alkyl, C1-C3—alkoxy, halogen—substituted C1-C3-alkyl (preferably perfluorinated C1-C3—alkyl (CF3, C2F5 or C3F7)), halogen-substituted C1-C3—alkoxy (preferably perfluorinated alkoxy (OCF3, OC2F5 or OC3F7)), C1-C3- alkylsulphanyl, C1-C3-alkylsulphinyl, C1-C3-alky1sulphonyl, fluorine, bromine or chlorine; is N or C-R3, preferably C-R3 in which is H, halogen, or optionally substituted C1—C4-alky1, preferably H, fluorine, chlorine or optionally n—substituted C1-C2-alkyl, more ably H or fluoro-substituted methyl, for example perfluoromethyl; is en, C1-C3-alkyl, Cl-Cg—alkoxy, halogen-substituted C1—C3-alky1 (preferably perfluorinated C1-C3-alkyl (CF3, C2F5 or C3F7)), n-substituted C1—C3-alk0xy (preferably perfluorinated C1-C3—alkoxy (OCF3, OCZFS or OC3F7)), C1-C3- alkylsulphanyl, C1—C3-alkylsulphinyl, C1—C3-alkylsulphonyl, fluorine, chlorine or bromine, ably fluorine, ne, bromine, C1-C2-alkyl, halogen-substituted C1—C2- alkyl (e.g. perfluoromethyl) or optionally halogen-substituted C1-C2-alkoxy, more preferably e, e, chlorine, methyl, ethyl, fluorinated methyl or fluorinated ethyl (more preferably perfluoromethyl or perfluoroethyl), fluorinated methoxy or fluorinated ethoxy (more preferably perfluoromethoxy); is halogen or optionally halogen-substituted C1-C4-alkyl or optionally halogen- substituted C1-C4-alkoxy, preferably halogen-substituted C1—C3-alkyl or halogen- substituted Cl-Cg—alkoxy, more preferably halogen-substituted C1-C3—alky1 such as fluorinated Cl-Cg-alkyl (e.g. ated C3-alkyl such as perfluoropropyl).
A further-preferred embodiment relates to nds of the formula (10) (T = T22) (10) in which R1, Q, W, A2, B1, B5, R2, R4, R5, R6, R7, R8, R9 and R11 are each defined as described herein, in which R1 represents H or in which R1 represents methyl.
VV’O EMS/067647 J! '1! PCT/EP20l4/O73795 A preferred embodiment relates to compounds of the formula (Io) in which w is O; Q is optionally substituted alkyl or optionally substituted C3-C6-cycloalkyl or an unsaturated 4-, 5- or 6-membered heterocyclic ring optionally substituted by one, two or three V substituents, where V is independently halogen, cyano, nitro, 0x0 (=0), optionally halogen-substituted Cl-Cs-alkyl, C1-C4-alkenyl, C1—C6-alkoxy, C1—C6- alkylsulphanyl, C1-C6—alky1sulphinyl, C1—C6-alkylsulphonyl; preferably halogen-substituted C1-C3-alkyl; with cyano, hydroxyl or carbonamide (—C(=O)N(R)2 where R is independently H or C1-C3-alkyl, tuted Cl-Cg—alkyl; C3- lkyl; cyano—substituted, halogen—substituted, nitro-substituted or halogenated C1- Cg-alkyl-substituted C3-cycloa1kyl; an unsaturated 4—, 5- or 6-membered heterocyclic ring optionally substituted by one, two or three V and containing one or two heteroatoms selected from a group ting of N, O and S, where V is independently n, cyano, nitro, 0x0 (=0), optionally halogen-substituted C1-C6—alkyl; more preferably fluorinated C1—C3—alky1 such as CF3, CHchg 0r CH2CH2CF3; C1-C3- alkyl substituted by carbonamide (—C(=O)N(R)2 where R is independently H, C1-C3— alkyl or halogen-substituted C1-C3-alkyl), such as 2-0xo—2-(2,2,2- trifluoroethylamino)ethyl; cyclopropyl; cyano-substituted or fluorinated C1-C2-alkyl- substituted cyclopropyl such as l-(cyano)cyclopropyl or 1- 2O (trifluoromethyl)cyclopropyl); a 4-membered heterocyclic ring ning one atom selected from a group consisting ofN, O and S, such as thietan—3—yl; R7 and R9 are each H; in each case is H; is H; is H, halogen or C1-C4—alkyl, preferably H, fluorine, chlorine or methyl; is H or halogen, preferably H, fluorine or chlorine; is H or halogen, ably H, fluorine 0r chlorine; is N or C—Rlo, preferably C-R10 in which is hydrogen, C1-C3-alkyl, C1—C3-alkoxy, halogen-substituted C1-C3-alkyl (preferably rinated alkyl (CF3, C2F5 or C3F7)), halogen—substituted C1-C3—alkoxy (preferably perfluorinated C1-C3—alkoxy (OCF3, OCZFS or OC3F7)), C1—C3- alkylsulphanyl, C1-C3-alkylsulphinyl, C1-C3—alkylsulph0nyl, fluorine, bromine or chlorine; is N or C-R3, ably C-R3 in which is H, halogen, or ally substituted C1-C4-alkyl, preferably H, fluorine, ne or optionally halogen—substituted C1-C2-alkyl, more preferably H or fluoro—substituted methyl, for example perfluoromethyl; W0 ZOE/067647 — 56 — PCT/EP2014/G7379Ul R6 is en, alkyl, C1—C3-alkoxy, halogen-substituted C1—C3-alky1 (preferably perfluorinated C1—C3—alkyl (C133, C2135 or C3F7)), n-substituted C1-C3-alkoxy (preferably perfluorinated C1-C3—alkoxy (OCF3, OC2F5 or OC3F7)), C1-C3— alkylsulphanyl, C1-C3-alkylsulphinyl, C1-C3-alkylsulphonyl, fluorine, chlorine or bromine, preferably fluorine, chlorine, bromine, C1-C2—alkyl, halogen-substituted C1-C2- alkyl (e.g. perfluoromethyl) or optionally halogen-substituted C1-C2—alkoxy, more preferably e, bromine, chlorine, methyl, ethyl, fluorinated methyl or fluorinated ethyl (more preferably perfluoromethyl or perfluoroethyl), fluorinated methoxy or fluorinated ethoxy (more preferably perfluoromethoxy); R8 is halogen or optionally halogen—substituted C1-C4-alkyl or optionally halogen- substituted C1-C4—alkoxy, preferably halogen-substituted C1-C3-alkyl or halogen— substituted C1-C3-alkoxy, more preferably halogen-substituted alkyl such as fluorinated C1-C3-alkyl (e.g. fluorinated C3-alkyl such as perfluoropropyl).
A preferred embodiment relates to compounds of the formula (10) in which w is O; Q is optionally substituted C1-C4—alkyl or optionally substituted C3-C6-cycloalkyl or an unsaturated 4-, 5- or 6-membered heterocyclic ring optionally substituted by one, two or three V tuents, where V is independently halogen, cyano, nitro, oxo (=0), optionally halogen—substituted C1—C6-alkyl, alkenyl, C1—C6-alkoxy, C1—C6- alkylsulphanyl, C1-C6—alkylsulphinyl, C1-C6-alkylsulphonyl; preferably halogen-substituted C1-C3-alkyl; with cyano, hydroxyl or carbonamide (-C(=O)N(R)2 where R is independently H or C1—C3—alkyl, substituted alkyl; C3- cycloalkyl; cyano-substituted, n—substituted, substituted or halogenated C1- CZ-alkyl-substituted Cg-cycloalkyl; an rated 4-, 5- or 6-membered heterocyclic ring optionally substituted by one, two or three V and containing one or two heteroatoms selected from a group consisting of N, O and S, where V is independently halogen, cyano, nitro, oxo (=0), optionally halogen-substituted C1-C5—alkyl; more preferably fluorinated alkyl such as CF3, CHZCF3 or CHZCHZCFg; Cl-C3— alkyl substituted by carbonamide (—C(=O)N(R)2 Where R is ndently H, C1-C3- alkyl or halogen-substituted C1-C3—alkyl), such as 2-oxo—2-(2,2,2- trifluoroethylamino)ethyl; cyclopropyl; cyano—substituted or fluorinated C1-C2—alkyl- substituted cyclopropyl such as l —(cyano)cyclopropyl or 1 - (trifluoromethyl)cyclopropyl); a 4—membered heterocyclic ring containing one heteroatom ed from a group consisting of N, O and S, such as thietan-3 —yl; R7andR9 are each H; R11 in each case is H; R1 is methyl; W0 EMS/067647 'JI 7 - ZOM/07379S is H, halogen or C1—C4-alkyl, preferably H, fluorine, chlorine or methyl; is H or halogen, preferably H, fluorine or chlorine; is H or halogen, preferably H, fluorine or chlorine; is N or C-Rlo, preferably C-R10 in which is hydrogen, C1-C3-alkyl, C1-C3-alkoxy, halogen-substituted C1-C3—alkyl (preferably perfluorinated C1—C3-alkyl (CF3, Cst or C3F7)), halogen-substituted C1-C3-alk0xy (preferably perfluorinated C1-C3-alkoxy (OCF3, OC2F5 or ), C1-C3— alkylsulphanyl, C1-C3-alkylsulphinyl, C1-C3-alkylsulphonyl, fluorine, bromine or chlorine; is N or C-R3, preferably C-R3 in which is H, halogen, or ally substituted C1-C4-alkyl, preferably H, fluorine, chlorine or optionally halogen—substituted C1-C2-alkyl, more preferably H or substituted methyl, for example romethyl; is hydrogen, C1-C3-alkyl, C1-C3-alkoxy, halogen-substituted C1-C3-alkyl (preferably perfluorinated C1-C3-alkyl (CF3, C2135 or C3F7)), halogen-substituted C1-C3-alkoxy rably perfluorinated C1-C3-alkoxy (OCF3, OC2F5 or 003F7)), C1—C3- alkylsulphanyl, C1-C3-alkylsulphinyl, alkylsulphonyl, fluorine, chlorine or bromine, preferably fluorine, chlorine, e, C1-C2-alkyl, halogen-substituted C1-C2— alkyl (e.g. perfluoromethyl) or optionally halogen-substituted C1-C2—alkoxy, more preferably e, e, chlorine, methyl, ethyl, fluorinated methyl or fluorinated ethyl (more preferably romethyl or perfluoroethyl), fluorinated methoxy or fluorinated ethoxy (more preferably perfluoromethoxy); is halogen or optionally halogen-substituted C1-C4-alkyl or optionally halogen- substituted Cl-C4—alkoxy, preferably halogen-substituted C1-C3—alkyl or halogen- substituted Cl-C3-alkoxy, more preferably halogen-substituted C1—C3—alkyl such as fluorinated C1-C3-alkyl (e.g. fluorinated C3-alkyl such as perfluoropropyl).
Examples of compounds of the formula (I) include the following structures: 2—chloro—N-cyclopropyl[1-[4-(1,l,l ,2,3,3 tafluoropropanyl)methy1—6- (trifluoromethyl)phenyl]-lH-pyrazol—4-yl]benzamide, ‘NO 2015/067647 — 58 — 2-chloro-N-(1-cyanocyclopropy1[1 ,1,1 ,2,3 ,3,3-heptafluoropropan—2—y1)methy1—6- (trifluoromethyl)pheny1]-1H-pyrazoly1]benzamide, 2—chloro-N-cyclopr0py1-5 -[4-[2,6-dimethy1[1 ,2,2,2-tetraflu0ro—1 - (trifluoromethyl)ethyl]phenyl]pyrazol-1 -y1]benzamide, 2-chloro-N-(1—cyanocyclopropy1)—5-[4-[2,6-dich10ro[1,2,2,2-tetrafluoro~1- (trifluoromethyl)ethyl]pheny1]pyrazol-1 -y1]benzamide, 2—ch10ro[3-[2-ch10ro[1,2,2,2—tetrafluoro(trifluoromethy1)ethy1]—6- (trifluoromethyl)phenyl]isoxazol-S-_y1]-N-cyclopropy1benzamide, - 59 » PCT/EPZUM/(ITS795 2-chlor0-N-(1-cyanocyclopropy1)—5-[3-[2-methy1[1,2,2,2-tetrafluor0(trifluoromethyl)ethyl] (trifluoromethyl)phenyl]isoxazol—S —yl]benzamide, Further inventive compounds are 2-chloro-N—(1-cyanocyclopropy1)[1-[2,6-dich10ro[1,2,2,2-tetrafluoro (trifluoromethyl)ethyl]phenyl]pyrrol-3 -yl]benzamide, 2-ch10ro[3 -[2—ch10r0-4—[1 ,2,2,2-tetrafluoro(triflu0romethy1)ethyl] (trifluoromethy1)phenyl]pyrrol-1 —cyclopropylbenzamide.
R] Methyl A preferred ment relates to compounds of the formula (I) in which R1 is methyl and all the other parameters are as defined in aph [85].
T3 — Methyl id="p-158" id="p-158" id="p-158" id="p-158" id="p-158" id="p-158"
[158] A further preferred embodiment relates to compounds of the formula (I) in which R1 is methyl, T is T3, R11 in T3 is H, W is O and all the other parameters are as defined in paragraph [85] and paragraph [1 12].
A further preferred embodiment relates to compounds of the formula (I) in which R1 is methyl, T is T3, R" in T3 is H, Wis 0, A1 is CR2, A2 is CR3 or N, A3 is CR4, A4 is CR5, B1 is CR6, B2 is CR7, 33 W0 2015/067647 — 60' - PCT/EPZUM/07379S is CR8, B4 is CR9, B5 is CR10 and all the other parameters are as defined in paragraph [85] and paragraph [1 12].
A further preferred embodiment relates to nds of the a (I) in which R1 is methyl, T is T3, R" in T3 is H, W is 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CR"), where R6 and R10 are each a tuent selected from halogen (preferably chlorine, bromine or fluorine), C1-C3-alkyl, halogen—substituted C1-C3-a1ky1, a1koxy or halogen- substituted C1-C3-alkoxy, and all the other parameters are as defined in paragraph [85] and paragraph [1 12].
A further preferred embodiment relates to compounds of the formula (I) in which R1 is methyl, T is T3, R" in T3 is H, w is 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CRIO, where R6 and R10 are each a substituent selected from n (preferably ne, bromine or fluorine), C1-C3-alky1, halogen-substituted alkyl, C1-C3-a1koxy or n- substituted C1-C3—alkoxy, and all the other parameters are as defined in paragraph [85] and paragraph [1 12].
T2 - Methyl A further preferred embodiment relates to compounds of the formula (I) in which R1 is methyl, T is T2, R11 in T2 is H, W is O and all the other parameters are as defined in paragraph [85] and paragraph [112].
A further preferred embodiment relates to compounds of the formula (I) in which R1 is methyl, T is T2,R11 in T2 is H, W is 0, A1 is CR2, A2 is CR3 or N, A3 is CR4, A4 is CR5, B1 is CR6, B2 is CR7, B3 is CR8, B4 is CR9, B5 is CR10 and all the other parameters are as defined in paragraph [85] and paragraph [1 12].
A further preferred embodiment relates to nds of the formula (I) in which R1 is methyl, T is T2,R11 in T2 is H, W is 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, 32 is CH, B3 is CR8, B4 is CH, B5 is CR"), where R6 and R10 are each a tuent selected from halogen rably chlorine, bromine or fluorine), C1-C3—alky1, halogen-substituted C1-C3-alkyl, C1-C3-alkoxy or halogen- substituted C1-C3-alkoxy, and all the other parameters are as defined in paragraph [85] and paragraph [1 12].
A further preferred embodiment relates to compounds of the formula (1) in which R1 is methyl, T is T2, R" in T2 is H, w is 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is CH, 133 is CR8, B4 is CH, B5 is CRIO, where R6 and R10 are each a substituent selected from halogen (preferably ne, bromine or fluorine), C1-C3—a1kyl, halogen-substituted C1—C3-alkyl, C1—C3-alkoxy or halogen- substituted C1—C3—a1koxy, and all the other parameters are as defined in paragraph [85] and paragraph [1 12].
‘WO EMS/067647 - 61 — f’CT/EP2014/(I73795 T4 - Methyl A further preferred embodiment relates to compounds of the formula (I) in which R1 is methyl, T is T4, R11 in T4 is H, W is O and all the other parameters are as defined in paragraph [85] and paragraph [112].
A further preferred embodiment relates to compounds of the formula (I) in which R1 is methyl, T is T4,R11 in T4 is H, W is 0, A1 is CR2, A2 is CR3 or N, A3 is CR4, A4 is CR5, B1 is CR6, B2 is CR7, B3 is CR8, B4 is CR9, B5 is CR10 and all the other parameters are as defined in paragraph [85] and paragraph [1 12].
A further preferred embodiment relates to compounds of the formula (I) in which R1 is methyl, T is T4, R11 in T4 is H, W is 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is Ch, B3 is CR8, B4 is CH, B5 is CR"), where R6 and R10 are each a substituent selected from halogen (preferably chlorine, bromine or fluorine), C1—C3-a1kyl, halogen-substituted C1-C3-alkyl, alkoxy or halogen- substituted C1-C3—alkoxy, and all the other parameters are as defined in paragraph [85] and paragraph [1 12]. id="p-169" id="p-169" id="p-169" id="p-169" id="p-169" id="p-169"
[169] A further preferred embodiment s to compounds of the formula (I) in which R1 is methyl, T is T4,R11 in T4 is H, W is 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CRIO, where R6 and R10 are each a tuent selected from halogen (preferably chlorine, bromine or fluorine), C1-C3-alkyl, halogen-substituted alkyl, C1-C3-alkoxy or n- substituted C1-C3-alkoxy, and all the other parameters are as defined in paragraph [85] and aph [1 12].
T22 — Methyl A further preferred embodiment relates to compounds of the formula (I) in which R1 is methyl, T is T22, R11 in T22 is H, W is O and all the other parameters are as defined in paragraph [85] and paragraph [112]. id="p-171" id="p-171" id="p-171" id="p-171" id="p-171" id="p-171"
[171] A r red embodiment relates to compounds of the formula (I) in which R1 is methyl, T is T22,R11 in T22 is H, W is 0, A1 is CR2, A2 is CR3 or N, A3 is CR4, A4 is CR5, B1 is CR6, B2 is CR7, B3 is CR8, B4 is CR9, B5 is CR10 and all the other parameters are as defined in paragraph [85] and paragraph [112].
A r preferred embodiment relates to compounds of the formula (I) in which R1 is methyl, 3O T is T22, R" in T22 is H, W is 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CR"), where R6 and R10 are each a substituent selected from halogen (preferably chlorine, bromine or fluorine), C1-C3-a1kyl, n-substituted C1—C3-alkyl, C1-C3-alkoxy or halogen- substituted C1—C3—a1koxy, and all the other parameters are as defined in aph [85] and paragraph [1 12]. » 6: — A further preferred embodiment relates to compounds of the formula (I) in which R1 is , T is T22, R" in T22 is H, W is 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CRIO, where R6 and R10 are each a substituent selected from halogen (preferably chlorine, bromine or fluorine), C1-C3-alkyl, halogen-substituted C1—C3-alkyl, alkoxy or n- substituted C1-C3-alkoxy, and all the other parameters are as defined in paragraph [85] and paragraph [1 12].
T23 — Methyl A further preferred embodiment s to compounds of the formula (I) in which R1 is methyl, T is T23, R11 in T23 is H, W is O and all the other parameters are as defined in paragraph [85] and paragraph [0113] et seq.
A further preferred embodiment relates to compounds of the formula (I) in which R1 is methyl, T is T23,R11 in T23 is H, w is 0, A1 is CR2, A2 is CR3 or N, A3 is CR4, A4 is CR5, B1 is CR6, B2 is CR7, B3 is CR8, B4 is CR9, B5 is CR10 and all the other parameters are as defined in paragraph [85] and paragraph [0113] et seq. id="p-176" id="p-176" id="p-176" id="p-176" id="p-176" id="p-176"
[176] A further preferred embodiment relates to compounds of the formula (I) in which R1 is methyl, T is T23,R11 in T23 is H, Wis 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CRIO, where R6 and R10 are each a substituent selected from halogen (preferably chlorine, bromine or e), C1-C3-alkyl, halogen-substituted C1—C3-alkyl, C1-C3-alkoxy or halogen- substituted C1—C3-a1koxy, and all the other parameters are as defined in paragraph [85] and aph id="p-113" id="p-113" id="p-113" id="p-113" id="p-113" id="p-113"
[0113] et seq.
A further preferred ment relates to compounds of the formula (I) in which R1 is methyl, T is T23, R11 in T23 is H, W is 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CR"), where R6 and R10 are each a substituent selected from halogen (preferably chlorine, bromine or fluorine), C1-C3-a1kyl, halogen-substituted alkyl, C1-C3-alkoxy or halogen- substituted C1—C3-alkoxy, and all the other parameters are as defined in paragraph [85] and paragraph et seq.
T3-H A preferred embodiment relates to compounds of the formula (I) in which R1 is en (H) and all the other parameters are as defined in paragraph [0113] et seq. id="p-179" id="p-179" id="p-179" id="p-179" id="p-179" id="p-179"
[179] A further preferred embodiment relates to compounds of the formula (I) in which R1 is H, T is T3, R11 in T3 is H, W is O and all the other parameters are as defined in paragraph [85] and paragraph et seq.
A further red embodiment relates to nds of the formula (I) in which R1 is H, T is T3, R" in T3 is H, Wis 0, A1 is CR2, A2 is CR3 or N, A3 is CR4, A4 is CR5, B1 is CR6, B2 is CR7, B3 is VCO 2(115/067647 - 63 — S CR8, B4 is CR9, B5 is CR10 and all the other ters are as defined in paragraph [85] and paragraph et seq.
A further preferred embodiment relates to compounds of the formula (I) in which R1 is H, T is T3, R" in T3 is H, Wis 0, A1 is CH, A2 is CH or N, A, is CR4, A4 is CH, B1 is CR6, B2 is CH, B, is CR8, B4 is CH, B5 is CR"), where R6 and R10 are each a substituent selected from halogen (preferably chlorine, bromine or fluorine), C1-C3-alkyl, n-substituted C1-C3-alkyl, C1-C3—alkoxy or halogen- substituted C1-C3-alkoxy, and all the other parameters are as defined in paragraph [85] and paragraph et seq.
A further red embodiment relates to compounds of the formula (I) in which R1 is H, T is T3, R11 in T3 is H, W is 0, A1 is CH, A2 is CH or N, A, is CR4, A4 is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CRIO, where R6 and R10 are each a substituent selected from halogen (preferably chlorine, bromine or fluorine), C1—C3-alkyl, halogen-substituted alkyl, C1-C3-alkoxy or halogen- tuted C1-C3-alkoxy, and all the other parameters are as defined in paragraph [85] and paragraph et seq.
TZ-H A further preferred embodiment relates to compounds of the formula (I) in which R1 is H, T is T2, R11 in T2 is H, W is O and all the other parameters are as defined in aph [85] and paragraph et seq.
A r preferred embodiment relates to compounds of the formula (I) in which R1 is H, T is r2, R" in T2 is H, Wis 0, A1 is CR2, A2 is CR3 or N, A, is CR4, A4 is CR5, B1 is CR6, B2 is CR7, B, is CR8, B4 is CR9, B5 is CR10 and all the other parameters are as defined in paragraph [85] and paragraph et seq.
A further preferred embodiment relates to compounds of the formula (I) in which R1 is H, T is T2, R" in T2 is H, Wis 0, A1 is CH, A2 is CH or N, A, is CR4, A4 is CH, B1 is CR6, B2 is CH, B, is CR8, B4 is CH, B5 is CR"), where R6 and R10 are each a substituent selected from halogen (preferably chlorine, e or fluorine), C1—C3-alkyl, halogen-substituted C1-C3—alkyl, C1-C3—alk0xy or halogen- substituted alkoxy, and all the other parameters are as defined in paragraph [85] and paragraph et seq.
A further red embodiment relates to compounds of the formula (I) in which R1 is H, T is 3O T2, R" in T2 is H, Wis 0, A1 is CH, A2 is CH or N, A, is CR4, A4 is CH, B1 is CR6, B2 is CH, B, is CR8, B4 is CH, B5 is CRIO, where R6 and R10 are each a substituent selected from n (preferably chlorine, bromine or fluorine), C1—C3-alkyl, halogen-substituted C1-C3-alkyl, C1-C3-alkoxy or halogen— substituted C1-C3—alkoxy, and all the other parameters are as defined in paragraph [85] and paragraph et seq. ‘ - 64 ~ T4-H A further preferred embodiment relates to compounds of the formula (I) in which R1 is H, T is T4, R" in T4 is H, W is O and all the other parameters are as defined in paragraph [85] and paragraph et seq.
A r preferred embodiment relates to compounds of the formula (I) in which R1 is H, T is T4, R" in T4 is H, Wis 0, A1 is CR2, A2 is CR3 or N, A3 is CR4, A4 is CR5, B1 is CR6, B2 is CR7, B3 is CR8, B4 is CR9, B5 is CR10 and all the other parameters are as defined in paragraph [85] and paragraph et seq.
A further preferred embodiment s to compounds of the formula (I) in which R1 is H, T is T4, R" in T4 is H, W is 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CRIO, where R6 and R10 are each a substituent selected from halogen (preferably chlorine, bromine or fluorine), C1-C3-alkyl, halogen-substituted C1—C3-alkyl, C1-C3-alkoxy or halogen- substituted alkoxy, and all the other parameters are as defined in paragraph [85] and paragraph et seq. id="p-190" id="p-190" id="p-190" id="p-190" id="p-190" id="p-190"
[190] A further preferred embodiment relates to compounds of the formula (I) in which R1 is H, T is T4, R" in T4 is H, W is 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CR"), where R6 and R10 are each a substituent selected from halogen (preferably chlorine, bromine or e), C1-C3-alkyl, halogen-substituted C1-C3-alkyl, C1—C3—alkoxy or halogen- substituted C1-C3-alkoxy, and all the other parameters are as defined in aph [85] and paragraph id="p-113" id="p-113" id="p-113" id="p-113" id="p-113" id="p-113"
[0113] et seq.
T22-H A further preferred embodiment relates to compounds of the formula (I) in which R1 is H, T is T22, R11 in T22 is H, W is O and all the other parameters are as defined in paragraph [85] and paragraph et seq. id="p-192" id="p-192" id="p-192" id="p-192" id="p-192" id="p-192"
[192] A further red embodiment s to compounds of the formula (I) in which R1 is H, T is T22, R" in T22 is H, w is 0, A1 is CR2, A2 is CR3 or N, A3 is CR4, A4 is CR5, B1 is CR6, B2 is CR7, B3 is CR8, B4 is CR9, B5 is CR10 and all the other parameters are as defined in paragraph [85] and paragraph et seq.
A further preferred embodiment relates to compounds of the formula (I) in which R1 is H, T is T22, R" in T22 is H, w is 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CRIO, where R6 and R10 are each a tuent selected from halogen (preferably chlorine, bromine or fluorine), C1-C3-alkyl, halogen-substituted C1-C3-alkyl, C1-C3-alkoxy or halogen- substituted C1-C3-alkoxy, and all the other parameters are as defined in aph [85] and paragraph et seq. "’0 2015/067647 - 65 — A further prefeired embodiment relates to compounds of the a (I) in which R1 is H, T is T22, R" in T22 is H, Wis 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, BI is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CR"), where R6 and R10 are each a substituent selected from halogen (preferably chlorine, e or fluorine), C1-C3-alkyl, halogen-substituted C1—C3-alkyl, C1-C3—alkoxy or halogen- substituted C1-C3-alkoxy, and all the other ters are as defined in paragraph [85] and paragraph et seq.
T23 —H A further preferred embodiment relates to compounds of the formula (I) in which R1 is H, T is T23, R11 in T23 is H, W is O and all the other parameters are as defined in paragraph [85] and paragraph id="p-113" id="p-113" id="p-113" id="p-113" id="p-113" id="p-113"
[0113] et seq.
A r red embodiment relates to compounds of the formula (I) in which R1 is H, T is T23, R" in T23 is H, W is 0, A1 is CR2, A2 is CR3 or N, A3 is CR4, A4 is CR5, B1 is CR6, B2 is CR7, B3 is CR8, B4 is CR9, B5 is CR10 and all the other parameters are as defined in paragraph [85] and paragraph et seq. id="p-197" id="p-197" id="p-197" id="p-197" id="p-197" id="p-197"
[197] A further red embodiment relates to compounds of the formula (I) in which R1 is H, T is T23, R11 in T23 is H, W is 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CRIO, where R6 and R10 are each a substituent selected from halogen (preferably chlorine, bromine or fluorine), C1-C3-alkyl, n-substituted C1-C3-alkyl, C1-C3—alkoxy or halogen- substituted C1-C3-alkoxy, and all the other ters are as defined in paragraph [85] and paragraph id="p-113" id="p-113" id="p-113" id="p-113" id="p-113" id="p-113"
[0113] et seq.
A r preferred embodiment s to compounds of the formula (I) in which R1 is H, T is T23,R11 in T23 is H, Wis 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CR"), where R6 and R10 are each a substituent selected from halogen (preferably chlorine, bromine or fluorine), alkyl, halogen-substituted C1-C3-alkyl, C1-C3-alkoxy or halogen- substituted C1-C3-alkoxy, and all the other ters are as defined in paragraph [85] and paragraph et seq.
A further preferred embodiment relates to compounds of the formula (I) in which B1 is C-R6 and R6 is halogen (preferably chlorine or fluorine), C1—C4-alkyl, C1-C4—alkoxy, C1-C4-haloalkyl (preferably perfluorinated C1-C4-alkyl), C1-C4-haloalkoxy (preferably perfluorinated C1-C4-alkoxy), C1-C4- alkylsulphanyl or C1—C4—alkylsu1phonyl.
Salts of the inventive compounds that are suitable in accordance with the invention, for example salts with bases or acid addition salts, are all customary non-toxic salts, preferably agriculturally and/or physiologically acceptable salts. Preference is given to salts with inorganic bases, for example alkali metal salts (e.g. sodium, potassium or m salts), alkaline earth metal salts (e.g. calcium or "’0 2015/067647 — 66 — magnesium salts), ammonium salts or salts with organic bases, in particular with organic amines, for example triethylammonium, dicyclohexylammonium, N,N’-dibenzylethylenediammonium, pyridinium, picolinium or ethanolammonium salts, salts with inorganic acids (e.g. hlorides, romides, dihydrosulphates, rosulphates or phosphates), salts with c carboxylic acids or organic sulpho acids (e.g. forrnates, acetates, trifluoroacetates, maleates, tartrates, methanesulphonates, benzenesulphonates or 4-toluenesulphonates). It is well known that es, for example some of the inventive compounds, are capable of forming N—oxides, which are likewise inventive salts. ing on the nature of the substituents, the compounds of the formula (I) may be in the form of geometric and/or lly active isomers or corresponding isomer mixtures in different compositions. These stereoisomers are, for example, enantiomers, diastereomers, atropisomers or ric isomers. Accordingly, the invention encompasses both pure stereoisomers and any mixtures of these isomers.
The invention also relates to s for controlling animal pests, in which nds of the formula (I) are d to act on animal pests and/or their habitat. The control of the animal pests is preferably conducted in agriculture and forestry, and in material protection. ably excluded from this are methods for the surgical or therapeutic treatment of the human or animal body and diagnostic methods carried out on the human or animal body.
The ion further relates to the use of the compounds of the formula (I) as pesticides, especially crop protection agents. id="p-204" id="p-204" id="p-204" id="p-204" id="p-204" id="p-204"
[204] In the context of the present application, the term "pesticide" also always encompasses the term "crop protection agent".
The compounds of the formula (I), given good plant tolerance, favourable homeotherm toxicity and good environmental compatibility, are suitable for protecting plants and plant organs against biotic and abiotic stress factors, for increasing harvest yields, for improving the quality of the harvested material and for controlling animal pests, especially insects, arachnids, helminths, nematodes and molluscs, which are encountered in lture, in horticulture, in animal husbandry, in aquatic cultures, in forests, in s and leisure facilities, in the protection of stored products and of materials, and in the hygiene sector. They can preferably be used as pesticides. They are effective against normally sensitive and resistant species and against all or some stages of development. The abovementioned pests include: pests from the phylum of the Arthropoda, especially from the class of the ida, for example Acarus spp., for example Acarus siro, Aceria kuko, Aceria sheldoni, Aculops spp., Aculus spp., for e Aculus fockeui, Aculus schlechtendali, Amblyomma spp., Amphitetranychus viennensis, Argas spp., lus spp., Brevipalpus spp., for example Brevipalpus phoenicis, Bryobia graminum, Bryobia praetiosa, Centruroides spp., Chorioptes spp., Dermanyssus gallinae, Dermatophagoides Vt’O‘ 2015/067647 — 67 - pteronyssinus, Dermatophagoides farinae, Dermacentor spp., Eotetranychus spp., for example Eotetranychus hicon'ae, Epitrimerus pyri, Eutetranychus spp., for example Eutetranychus banksi, Eriophyes spp., for example Eriophyes pyri, Glycyphagus domesticus, Halotydeus destructor, Hemitarsonemus spp., for example Hemitarsonemus latus (=Polyphagotarsonemus latus), Hyalomma spp., Ixodes spp., Latrodectus spp., Loxosceles spp., mbicula autumnalis, Nuphersa spp., Oligonychus spp., for example Oligonychus coniferarum, Oligonychus ilicis, Oligonychus indicus, Oligonychus mangiferus, Oligonychus pratensis, Oligonychus punicae, Oligonychus yothersi, Ornithodorus spp., Ornithonyssus spp., Panonychus spp., for example Panonychus citri (=Metatetranychus citri), Panonychus ulmi (=Metatetranychus ulmi), coptruta oleivora, Platytetranychus multidigituli, Polyphagotarsonemus latus, Psoroptes spp., Rhipicephalus spp., Rhizoglyphus Steneotarsonemus , spp., Sarcoptes spp., o , tarsonemus spp., Tarsonemus for spp., for example Tarsonemus confusus, Tarsonemus pallidus, ychus spp., example Tetranychus canadensis, Tetranychus cinnabarinus, Tetranychus turkestani, Tetranychus urticae, cula alfreddugesi, Vaejovis spp., Vasates lycopersici; from the class of the Chilopoda, for example Geophilus spp., era spp.; from the order or the class of the Collembola, for e Onychiurus armatus; Sminthurus Viridis; from the class of the Diplopoda, for example lus guttulatus; from the class of the Insecta, for example from the order of the Blattodea, for e Blatta orientalis, lla asahinai, Blattella germanica, Leucophaea maderae, Panchlora spp., Parcoblatta spp., Periplaneta spp., for example Periplaneta americana, Periplaneta australasiae, Supella longipalpa; from the order of the Coleoptera, for example Acalymma vittatum, Acanthoscelides obtectus, us spp., Agelastica alni, Agriotes spp., for example Agriotes linneatus, Agriotes mancus, Alphitobius inus, Amphimallon solstitialis, Anobium punctatum, Anoplophora spp., Anthonomus spp., for example Anthonomus grandis, Anthrenus spp., Apion spp., Apogonia spp., Atomaria spp., for example Atomaria linearis, Attagenus spp., Ban's caerulescens, Bruchidius obtectus, Bruchus spp., for example Bruchus pisorum, s rufimanus, Cassida spp., Cerotoma trifurcata, Ceutorrhynchus spp., for e Ceutorrhynchus assimihs, Ceutorrhynchus quadridens, Ceutorrhynchus rapae, Chaetocnema Cleonus spp., for example Chaetocnema confinis, Chaetocnema denticulata, Chaetocnema ectypa, mendicus, Conoderus spp., Cosmopolites spp., for example Cosmopolites sordidus, Costelytra dica, Ctenicera spp., Curculio spp., for example Curculio caryae, Curculio caryatrypes, Curculio obtusus, io sayi, Cryptolestes ferrugineus, Cryptolestes pusillus, rhynchus lapathi, Cryptorhynchus erae, Cylindrocopturus spp., Cylindrocopturus adspersus, Cylindrocopturus fiarnissi, Dermestes spp., Diabrotica spp., for example Diabrotica balteata, Diabrotica i, Diabrotica undecimpunctata howardi, Diabrotica undecimpunctata undecimpunctata, Diabrotica virgifera Virgifera, Diabrotica Virgifera zeae, Dichocrocis spp., Dicladispa armigera, Diloboderus spp., Epilachna spp., for example Epilachna borealis, Epilachna stis, Epitrix spp., for example Epitn'x cucumeris, Epitrix fuscula, Epitrix hiitipennis, Epitrix subcrinita, Epitrix tuberis, Faustinus spp., Gibbium psylloides, Gnathocerus cornutus, Hellula undalis, Heteronychus arator, nyx spp., Hylamorpha elegans, Hylotrupes s, Hypera a, Hypomeces squamosus, Hypothenemus spp., for e Hypothenemus hampei, Hypothenemus obscurus, Hypothenemus ens, Lachnostema consanguinea, Lasioderma serricorne, Latheticus oryzae, Lathridius spp., Lema spp., Leptinotarsa decemlineata, tera spp., for example Leucoptera coffeella, Lissorhoptrus oryzophilus, Lixus spp., Luperomorpha xanthodera, Luperodes spp., Lyctus spp., Megascelis spp., Melanotus spp., for example Melanotus longulus oregonensis, Meligethes aeneus, Melolontha spp., for example Melolontha melolontha, Migdolus xanthographus, Necrobia spp., Monochamus spp., Naupactus spp., Niptus hololeucus, Oryctes rhinoceros, Oryzaephilus surinamensis, Oryzaphagus oryzae, Otiorhynchus spp., for example Otiorhynchus cribricollis, Otiorhynchus ligustici, Otiorhynchus ovatus, Otiorhynchus rugosostriarus, ynchus us, Oxycetonia jucunda, Phaedon cochleariae, Phyllophaga spp., phaga ', Phyllotreta spp., for example Phyllotreta armoraciae, Phyllotreta a, Phyllotreta ramosa, Phyllotreta striolata, Popillia ca, Premnotrypes spp., Prostephanus tus, Psylliodes spp., for example Psylliodes affinis, Psylliodes chrysocephala, Psylliodes punctulata, Ptinus spp., Rhizobius lis, Rhizopertha dominica, Sitophilus spp., for example Sitophilus granarius, Sitophilus linearis, Sitophilus oryzae, Sitophilus zeamais, Sphenophorus spp., Stegobium paniceum, Sternechus spp., for example Sternechus paludatus, Symphyletes spp., Tanymecus spp., for example Tanymecus collis, Tanymecus indicus, cus palliatus, Tenebrio molitor, Tenebrioides anicus, Tribolium spp., for example Tribolium audax, Tribolium castaneum, Tribolium um, Trogoderma for example Zabrus tenebrioides; spp., Tychius spp., Xylotrechus spp., Zabrus spp., from the order of the Diptera, for example Aedes spp., for example Aedes aegypti, Aedes albopictus, Aedes sticticus, Aedes vexans, za spp., for example Agromyza frontella, Agromyza parvicornis, Anastrepha spp., les spp., for example Anopheles quadrimaculatus, les gambiae, Asphondylia spp., Bactrocera spp., for example Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera oleae, Bibio hortulanus, Calliphora ocephala, Calliphora Vicina, Ceratitis capitata, Chironomus spp., Chrysozona pluvialis, omya spp., inia for spp., Chrysomya spp., Chrysops spp., example Contarinia johnsoni, Contarinia nastur’tii, Contarinia ra, Contarinia schulzi, Contarinia cola, Contarinia tritici, Cordylobia anthropophaga, Cricotopus sylvestris, Culex spp., for example Culex pipiens, Culex quinquefasciatus, Culicoides spp., Culiseta spp., Cuterebra spp., Dacus oleae, Dasineura spp., for example Dasineura brassicae, Delia spp., for example Delia antiqua, Delia coarctata, Delia florilega, Delia platura, Delia radicum, Dermatobia hominis, Drosophila spp., for example Drosphila melanogaster, Drosophila suzukii, Echinocnemus spp., Fannia spp., Gasterophilus spp., Glossina spp., Haematopota spp., Hydrellia spp., Hydrellia griseola, Hylemya spp., Hippobosca spp., rma spp., Liriomyza spp., for example Liriomyza brassicae, Liriomyza huidobrensis, Liriomyza sativae, Lucilia spp., for example Lucilia cuprina, Lutzomyia spp., Mansonia spp., Musca spp., for example Musca domestica, Musca domestica Vicina, Oestrus spp., Oscinella frit, Paratanytarsus spp., VVO 2015/067647 - 69 — uterbomiella subcincta, Pegomya spp., for example Pegomya betae, Pegomya hyoscyami, Pegomya rubivora, Phlebotomus spp., Phorbia spp., Phormia spp., la casei, Prodiplosis spp., Psila rosae, Rhagoletis spp., for example Rhagoletis cingulata, Rhagoletis completa, Rhagoletis fausta, Rhagoletis indifferens, Rhagoletis mendax, Rhagoletis pomonella, Sarcophaga spp., Simulium spp., for example Simulium meridionale, Stomoxys spp., Tabanus spp., Tetanops spp., Tipula spp., for example Tipula paludosa, Tipula simplex; from the order of the Heteroptera, for example Anasa tristis, Antestiopsis spp., Boisea spp., Blissus spp., Calocoris spp., Campylomma livida, Cavelefius spp., Cimex spp., for example Cimex adjunctus, Cimex hemipterus, Cimex lectularius, Cimex pilosellus, Collaria spp., Creontiades dilutus, s piperis, Dichelops furcatus, Diconocoris hewetti, Dysdercus spp., Euschistus spp., for example Euschistus heros, Euschistus , Euschistus tristigmus, Euschistus variolarius, ster spp., orpha halys, Heliopeltis spp., s nobilellus, Leptocorisa spp., Leptocorisa varicorm's, Leptoglossus occidentalis, Leptoglossus phyllopus, Lygocoris spp., for example Lygocoris pabulinus, Lygus spp., for example Lygus elisus, Lygus hesperus, Lygus lineolaris, Macropes excavatus, Monalonion atratum, Nezara spp., for example Nezara viridula, Oebalus spp., Piesma quadrata, Piezodorus spp., for example Piezodorus guildinii, Psallus spp., cystalpersea, Rhodnius spp., rgella singularis, Scaptocoris castanea, Scotinophora spp., Stephanitis nashi, Tibraca spp., Triatoma spp.; from the order of the Homoptera, for example Acizzia acaciaebaileyanae, Acizzia dodonaeae, Acizzia uncatoides, Acrida turrita, Acyfihosipon spp., for example Acyrthosiphon pisum, Acrogonia spp., Aeneolamia Aleyrodes proletella, Aleurolobus spp., Agonoscena spp., barodensis, Aleurothrixus floccosus, Allocaridara malayensis, a spp., for example Amrasca bigutulla, Amrasca devastans, Anuraphis cardui, Aonidiella spp., for example Aonidiella aurantii, Aonidiella citrina, Aonidiella inornata, Aphanostigma piri, Aphis spp., for example Aphis craccivora, Aphis fabae, Aphis forbesi, Aphis glycines, Aphis gossypii, Aphis hederae, Aphis isensis, Aphis middletoni, Aphis nasturtii, Aphis nerii, Aphis pomi, Aphis spiraecola, Aphis Viburniphila, Arboridia apicalis, Arytaim'lla spp., ella spp., otus spp., for e Aspidiotus nerii, Atanus spp., Aulacorthum solani, Bemisia tabaci, Blastopsylla occidentalis, Boreioglycaspis melaleucae, Brachycaudus helichrysi, Brachycolus spp., Brevicoryne brassicae, Cacopsylla spp., for example Cacopsylla la, Calligypona marginata, Cameocephala fulgida, Ceratovacuna lanigera, Cercopidae, Ceroplastes spp., siphon folii, Chionaspis tegalensis, Chlorita onukii, Chondracris rosea, Chromaphis dicola, Chrysomphalus ficus, lina mbila, Coccomytilus halli, Coccus spp., for example Coccus idum, Coccus longulus, Coccus pseudomagnoliarum, Coccus viridis, Cryptomyzus ribis, Cryptoneossa spp., Ctenarytaina spp., Dalbulus spp., Dialeurodes citri, Diaphon'na citri, Diaspis spp., Drosicha spp., Dysaphis spp., for example Dysaphis apiifolia, Dysaphis plantaginea, Dysaphis tulipae, Dysmicoccus spp., Empoasca spp., for e Empoasca abrupta, Empoasca fabae, Empoasca maligna, ca solana, Empoasca stevensi, Eriosoma spp., for example Eriosoma americanum, Eriosoma lamgerum, Eriosoma pyricola, Erythroneura spp., Eucalyptolyma spp., Euphyllura spp., "’0 2015/067647 — 7O — Euscelis bilobatus, Ferrisia spp., Geoeoccus coffeae, Glycaspis spp., Heteropsylla cubana, Heteropsylla spinulosa, disca coagulata, Hyalopterus arundinis, terus pruni, Icerya spp., for e Icerya purchasi, Idiocerus spp., Laodelphax striatellus, Lecanium spp., for example spp., Idioscopus Lecanium corni (=Parthenolecanium corni), saphes spp., for example Lepidosaphes ulmi, Lipaphis erysimi, Macrosiphum spp., for example Macrosiphum euphorbiae, Macrosiphum lilii, Macrosiphum rosae, Macrosteles facifrons, Mahanarva spp., Melanaphis sacchari, Metcalfiella spp., Metopolophium dirhodum, Monellia costalis, Monelliopsis pecanis, Myzus spp., for example Myzus ascalonicus, Myzus cerasi, Myzus ligustri, Myzus omatus, Myzus persicae, Myzus nicotianae, Nasonovia ribisnigri, Nephotettix spp., for example Nephotettix ceps, Nephotettix nigropictus, Nilaparvata lugens, Oncometopia spp., Orthezia praelonga, Oxya chinensis, Pachypsylla spp., Parabemisia myricae, Paratrioza spp., for example Paratrioza cockerelli, oria spp., Pemphigus spp., for example Pemphigus bursarius, Pemphigus populivenae, Peregrinus maidis, Phenacoccus spp., for example Phenacoccus madeirensis, Phloeomyzus passerinii, Phorodon , Phylloxera spp., for example Phylloxera devastatrix, xera notabilis, Pinnaspis aspidistrae, Planococcus spp., for example Planococcus citri, Prosopidopsylla flava, ulvinaria pyriformis, Pseudaulacaspis pentagona, coccus spp., for example Pseudococcus calceolariae, Pseudococcus comstocki, Pseudococcus longispinus, Pseudococcus maritimus, Pseudococcus Viburni, Psyllopsis spp., Psylla spp., for example Psylla buxi, Psylla mall, Psylla pyri, Pteromalus spp., Pyrilla spp., Quadraspidiotus spp., for example Quadraspidiotus sregiae, Quadraspidiotus ostreaeformis, Quadraspidiotus perniciosus, a gigas, Rastrococcus spp., Rhopalosiphum spp., for e Rhopalosiphum maidis, osiphum oxyacanthae, Rhopalosiphum padi, Rhopalosiphum rufiabdominale, Saissetia spp., for example tia coffeae, Saissetia miranda, Saissetia neglecta, Saissetia oleae, Scaphoideus titanus, Schizaphis graminum, Selenaspidus latus, Sitobion avenae, Sogata spp., Sogatella furcifera, Sogatodes spp., cephala festina, Siphoninus phillyreae, Tenalaphara malayensis, Tetragonocephela for example Toxoptera ii, Toxoptera spp., Tinocallis caryaefoliae, Tomaspis spp., era spp., citricidus, Trialeurodes vaporariorum, Trioza spp., for example Tn'oza diospyri, Typhlocyba spp., Unaspis spp., Viteus Vitifolii, Zygina spp.; from the order of the Hymenoptera, for example Acromyrmex spp., Athalia spp., for example Athalia for example Hoplocampa rosae, Atta spp., Diprion spp., for example Diprion s, ampa spp., cookei, Hoplocampa inea, Lasius spp., Monomorium pharaonis, Sirex spp., Solenopsis invicta, Tapinoma spp., Urocerus spp., Vespa spp., for example Vespa crabro, Xeris spp.; from the order of the Isopoda, for example Armadillidium vulgare, Oniscus asellus, Porcellio scaber; from the order of the Isoptera, for example Coptotermes spp., for example Coptotermes formosanus, Cornitermes cumulans, Cryptotermes spp., Incisitermes spp., Microtermes obesi, termes spp., Reticulitermes spp., for example Reticulitermes flavipes, Reticulitermes hesperus; "’0 ZOE/067647 - 7l — 2014/073795 from the order of the Lepidoptera, for example Achroia grisella, Acronicta major, Adoxophyes spp., for example Adoxophyes orana, Aedia leucomelas, Agrotis spp., for example Agrotis segetum, Agrotis ipsilon, Alabama spp., for example Alabama argillacea, Amyelois transitella, Anarsia spp., Anticarsia spp., for example Anticarsia gemmatalis, Argyroploce spp., Barathra brassicae, Borbo a, Bucculatrix thurberiella, Bupalus piniarius, Busseola spp., Cacoecia spp., ilia theivora, Capua reticulana, Carpocapsa pomonella, Carposina nsis, Cheimatobia brumata, Chilo spp., for example Chilo plejadellus, Chilo suppressalis, Choristoneura spp., Clysia ambiguella, Cnaphalocerus spp., Cnaphalocrocis medinalis, sia spp., Conopomorpha spp., achelus spp., Copitarsia spp., Cydia spp., for example Cydia nigricana, Cydia pomonella, Dalaca noctuides, Diaphania spp., Diatraea saccharalis, Earias spp., Ecdytolopha aurantium, Elasmopalpus lignosellus, Eldana saccharina, Ephestia spp., for example Ephestia elutella, Ephestia kuehniella, Eplnotia spp., Epiphyas postvittana, Etiella for example Euproctis chrysorrhoea, Euxoa spp., spp., Eulia spp., Eupoecilia ambiguella, Euproctis spp., Feltia spp., Galleria mellonella, Gracillaria spp., Grapholitha spp., for example Grapholita molesta, Grapholita prunivora, Hedylepta spp., Helicoverpa spp., for e Helicoverpa armigera, Helicoverpa zea, Heliothis spp., for example Heliothis virescens, Hofmannophila pseudospretella, Homoeosoma spp., Homona spp., Hyponomeuta padella, ria flavofasciata, ma spp., Leucinodes orbonalis, Leucoptera spp., for example Leucoptera coffeella, Lithocolletis spp., for e Lithocolletis blancardella, Lithophane ata, Lobesia spp., for example a botrana, Loxagrotis albicosta, Lymantria spp., for example Lymantria dispar, Lyonetia spp., for example Lyonetia lla, Malacosoma neustria, Maruca testulalis, Mamestra brassicae, Melanitis leda, Mocis spp., Monopis obviella, Mythimna separata, Nemapogon cloacellus, Nymphula spp., Oiketicus spp., Oria spp., Orthaga Oulema oryzae, s flammea, spp., Ostrinia spp., for example Ostrinia nubilalis, Oulema melanopus, Parnara spp., Pectinophora spp., for example Pectinophora gossypiella, Perileucoptera spp., Phthorimaea for example spp., for example Phthorimaea operculella, Phyllocnistis citrella, Phyllonorycter spp., Phyllonorycter blancardella, Phyllonorycter crataegella, Piefis spp., for e Pieris rapae, Platynota stultana, Plodia interpunctella, Plusia spp., la xylostella (=Plutella pennis), Prays spp., Prodenia spp., Protoparce spp., Pseudaletia spp., for example Pseudaletia unipuncta, Pseudoplusia includens, Pyrausta nubilalis, Rachiplusia nu, Schoenobius spp., for example Schoenobius bipunctifer, Scirpophaga for example Scirpophaga ta, Scotia segetum, Sesamia for spp., spp., e Sesamia inferens, Sparganothis spp., Spodoptera spp., for example Spodoptera eradiana, tera exigua, Spodoptera frugiperda, Spodoptera praefica, Stathmopoda spp., Stomopteryx subsecivella, Synanthedon spp., Tecia solanivora, Thermesia gemmatalis, Tinea cloacella, Tinea pellionella, Tineola bisselliella, Tortrix spp., Tfichophaga ella, Trichoplusia spp., for example Trichoplusia ni, yza incertulas, Tuta absoluta, Virachola spp.; from the order of the Orthoptera or Saltatoria, for example Acheta domesticus, Dichroplus spp., Gryllotalpa for e Gryllotalpa gryllotalpa, Hieroglyphus spp., Locusta spp., for example spp., a migratoria, Melanoplus spp., for example Melanoplus devastator, Schistocerca gregaria; V‘JQ 67647 from the order of the Phthiraptera, for e Damalinia spp., opinus spp., Linognathus spp., Pediculus spp., Phylloxera vastatrix, Phthirus pubis, Trichodectes spp.; from the order of the Psocoptera, for example Lepinotus spp., Liposcelis spp.; from the order of the Siphonaptera, for example, Ceratophyllus spp., Ctenocephalides spp., for example Ctenocephalides canis, Ctenocephalides felis, Pulex irritans, Tunga penetrans, Xenopsylla cheopis; from the order of the optera, for example Anaphothrips obscurus, Baliothrips biformis, Drepanothrips reuten', Enneothrips flavens, iniella spp., for example Frankliniella fusca, Frankliniella occidentalis, Frankliniella schultzei, Frankliniella tritici, Frankliniella vaccinii, Frankliniella williamsi, Heliothrips spp., othrips femoralis, Rhipiphorothrips cruentatus, thn'ps spp., Taeniothrips cardamomi, Thiips spp., for example Thrips palmi, Thrips tabaci; from the order of the Zygentoma (= Thysanura), for e Ctenolepisma spp., Lepisma saccharina, Lepismodes inquilinus, bia domestica; from the class of the Symphyla, for example Scutigerella spp., for example erella immaculata; pests from the phylum of the Mollusca, for example from the class of the Bivalvia, for example Dreissena spp., and also from the class of the Gastropoda, for example Arion spp., for example Arion ater rufus, Biomphalaria spp., Bulinus spp., Deroceras spp., for example Deroceras laeve, Galba spp., Lymnaea spp., Oncomelania spp., Pomacea spp., Succinea spp.; animal parasites from the phyla of the Plathelminthes and Nematoda, for example Ancylostoma Ascaris spp., for example Ancylostoma duodenale, Ancylostoma ceylanicum, Ancylostoma braziliensis, Chabertia spp., Clonorchis spp., Cooperia spp., spp., Brugia malayi, Brugia timori, Bunostomum spp., Dicrocoelium spp., Dictyocaulus filaria, Diphyllobothrium latum, Dracunculus medinensis, Echinococcus granulosus, Echinococcus multilocularis, Enterobius vermicularis, Faciola spp., chus spp., Heterakis spp., Hymenolepis nana, Hyostrongulus spp., Loa Loa, Nematodirus spp., Oesophagostomum spp., Opisthorchis spp., Onchocerca us, Ostertagia spp., Paragonimus spp., Schistosomen Taenia spp., Strongyloides fuelleborni, Strongyloides ralis, Stronyloides spp., saginata, Taenia solium, Trichinella spiralis, Trichinella nativa, nella britovi, Trichinella nelsoni, Trichinella pseudopsiralis, Trichostrongulus spp., Trichuris ria, eria bancrofti; plant pests from the phylum of the Nematoda, i.e. phytoparasitic nematodes, especially Aglenchus spp., for example Aglenchus agricola, Anguina spp., for example Anguina tritici, Aphelenchoides Belonolaimus spp., for example Aphelenchoides arachidis, Aphelenchoides fragariae, Belonolaimus spp., for example Belonolaimus gracilis, laimus longicaudatus, nortoni, VVO 2015/067647 — 73 - PCT/EP2014/O73795 Bursaphelenchus spp., for example Bursaphelenchus cocophilus, Bursaphelenchus eremus, Bursaphelenchus xylophilus, Cacopaurus spp., for example Cacopaurus pestis, Criconemella spp., for example Criconemella curvata, Criconemella onoensis, Criconemella ornata, Criconemella rusium, Criconemella ax (= Mesocriconema xenoplax), Criconemoides spp., for e Criconemoides ferniae, Criconemoides onoense, emoides ornatum, Ditylenchus spp., for example Ditylenchus dipsaci, Dolichodorus spp., Globodera spp., for example era pallida, Globodera rostochiensis, tylenchus spp., for example tylenchus dihystera, Hemicriconemoides spp., Hemicycliophora example Heterodera spp., Heterodera spp., for Heterodera avenae, glycines, Heterodera tii, Hoplolaimus spp., Longidorus spp., for example Longidorus africanus, Meloidogyne spp., for example Meloidogyne chitwoodi, Meloidogyne fallax, Meloidogyne hapla, Meloidogyne incognita, Meloinema spp., Nacobbus spp., Neotylenchus spp., Paraphelenchus spp., Paratrichodorus spp., for example Paratrichodorus minor, Pratylenchus spp., for example Pratylenchus ans, Pseudohalenchus spp., Psilenchus spp., Punctodera spp., Quinisulcius spp., Radopholus spp., for example olus citrophilus, Radopholus similis, Rotylenchulus spp., Rotylenchus spp., Scutellonema spp., Subanguina spp., Trichodorus spp., for example Trichodorus s, Trichodorus primitivus, Tylenchorhynchus spp., for example Tylenchorhynchus tus, Tylenchulus spp., for example Tylenchulus semipenetrans, Xiphinema spp., for example Xiphinema index.
In addition, it is possible to control, from the sub-kingdom of the Protozoa, the order of the Coccidia, for example, Eimeria spp. id="p-211" id="p-211" id="p-211" id="p-211" id="p-211" id="p-211"
[211] The compounds of the formula (I) can optionally, at certain trations or application rates, also be used as herbicides, safeners, growth regulators or agents to improve plant properties, as microbicides or gametocides, for example as fungicides, antimycotics, icides, Virucides (including agents against Viroids) or as agents against MLO (mycoplasma—like organisms) and RLO ttsia-like sms). If appropriate, they can also be used as intermediates or sors for the synthesis of other active ingredients.
The present invention filrther relates to formulations and use forms prepared therefrom as pesticides, for example drench, drip and spray liquors, comprising at least one nd of the formula (I). In some cases, the use forms comprise further pesticides and/or adjuvants which improve , such as penetrants, e. g. vegetable oils, for example rapeseed oil, sunflower oil, mineral oils, for example paraffin oils, alkyl esters of vegetable fatty acids, for example rapeseed oil methyl ester or soya oil methyl ester, or alkanol alkoxylates and/or Spreaders, for example alkylsiloxanes and/or salts, for example organic or inorganic ammonium or onium salts, for example ammonium sulphate or diammonium hydrogenphosphate and/or ion promoters, for example dioctyl sulphosuccinate or hydroxypropyl guar polymers and/or humectants, for example glycerol and/or fertilizers, for example ammonium-, potassium- or phosphorus—containing fertilizers.
\K’O 2015/067647 - 7" - PCT/EP2014/G73795 Customary formulations for example, water-soluble liquids (SL), emulsion concentrates are, (EC), emulsions in water (EW), suspension concentrates (SC, SE, FS, OD), water-dispersible granules (WG), granules (GR) and capsule concentrates (CS); these and further possible formulation types are bed, for example, by Crop Life International and in Pesticide Specifications, Manual on development and use of FAO and WHO specifications for pesticides, FAO Plant Production and Protection Papers — 173, prepared by the FAO/WHO Joint Meeting on Pesticide cations, 2004, ISBN: 9251048576. The formulations, in addition to one or more compounds of the a (I), optionally comprise further emically active ingredients.
These are preferably formulations or use forms which comprise auxiliaries, for example extenders, solvents, spontaneity promoters, carriers, emulsifiers, dispersants, frost protectants, biocides, thickeners and/or further auxiliaries, for example adjuvants. An adjuvant in this context is a component which enhances the biological effect of the formulation, without the ent itself having any biological effect. es of adjuvants are agents which e ion, spreading, attachment to the leaf surface or penetration. id="p-215" id="p-215" id="p-215" id="p-215" id="p-215" id="p-215"
[215] These formulations are produced in a known manner, for example by mixing the compounds of the formula (I) with auxiliaries, for e extenders, solvents and/or solid rs and/or other auxiliaries, for example surfactants. The fOrmulations are produced either in suitable facilities or else before or during application.
Auxiliaries used may be substances suitable for imparting l properties, such as particular physical, technical and/0r biological ties, to the formulation of the compounds of the formula (I), such as spray or to the use forms prepared from these formulations (for example ready-to-use pesticides liquors or seed dressing products).
Suitable extenders for example, water, polar and nonpolar organic al liquids, for are, example from the classes of the aromatic and nonaromatic hydrocarbons (such as paraffins, alkylbenzenes, alkylnaphthalenes, chlorobenzenes), the alcohols and polyols (which may optionally also be tuted, etherified and/0r esterified), the s (such as acetone, cyclohexanone), esters ding fats and oils) and (poly)ethers, the unsubstituted and substituted amines, amides, lactams (such as N—alkylpyrrolidones) and lactones, the sulphones and sulphoxides (such as dimethyl sulphoxide). id="p-218" id="p-218" id="p-218" id="p-218" id="p-218" id="p-218"
[218] If the extender ed is water, it is also possible to use, for example, organic solvents as auxiliary solvents. Useful liquid solvents are essentially: aromatics such as xylene, toluene or alkylnaphthalenes, chlorinated aromatics or chlorinated aliphatic hydrocarbons such as benzenes, chloroethylenes or methylene chloride, aliphatic hydrocarbons such as cyclohexane or paraffins, for example mineral oil fractions, mineral and vegetable oils, alcohols such as butanol or glycol and their ethers and esters, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or VVO 2015/067647 - 7 L}! l cyclohexanone, strongly polar solvents such as ylfonnamide and dimethyl sulphoxide, and also water.
In ple, it is possible to use all suitable solvents. Examples of suitable solvents are ic hydrocarbons such as xylene, toluene or alkylnaphthalenes, chlorinated aromatic or aliphatic hydrocarbons such as chlorobenzene, chloroethylene or methylene chloride, aliphatic hydrocarbons such alcohols such as methanol, as cyclohexane, paraffins, mineral oil fractions, l and vegetable oils, ethanol, isopropanol, butanol or glycol and their ethers and esters, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, strongly polar solvents such as dimethyl sulphoxide, and water. id="p-220" id="p-220" id="p-220" id="p-220" id="p-220" id="p-220"
[220] In principle, it is possible to use all suitable carriers. Useful carriers especially include: for example ammonium salts and ground natural minerals such as s, clays, talc, chalk, quartz, lgite, montmorillonite or diatomaceous earth, and ground synthetic materials such as finely divided silica, alumina and natural or tic silicates, resins, waxes and/or solid fertilizers. Mixtures of such carriers can likewise be used. Useful rs for granules include: for example crushed and fractionated natural rocks such as calcite, marble, pumice, sepiolite, dolomite, and synthetic granules of inorganic and organic meals, and also granules of organic material such as sawdust, paper, coconut shells, corn cobs and tobacco stalks.
Liquefied gaseous extenders or ts can also be used. Particularly suitable extenders or carriers are those which are gaseous at ambient temperature and under atmospheric pressure, for e aerosol propellant gases, such as halohydrocarbons, and also butane, propane, nitrogen and carbon dioxide.
Examples of emulsifiers and/or foam generators, dispersants or wetting agents having ionic or nonionic ties, or mixtures of these surfactants, are salts of polyacrylic acid, salts of lignosulphonic acid, salts of phenolsulphonic acid or naphthalenesulphonic acid, ndensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty amines, with substituted phenols (preferably henols or arylphenols), salts of sulphosuccinic esters, e derivatives (preferably alkyl taurates), phosphoric esters of polyethoxylated alcohols or phenols, fatty acid esters of polyols, and derivatives of the compounds comprising tes, sulphonates and phosphates, e.g. alkylaryl polyglycol , alkylsulphonates, alkyl sulphates, arylsulphonates, protein hydrolysates, lignosulphite waste liquors, and methyl cellulose. The presence of a surfactant is advantageous if one of the compounds of the formula (I) and/or one of the inert carriers is insoluble in water and when the application takes place in water. r aries which may be present in the formulations and the use forms derived rom include dyes such as inorganic pigments, for example iron oxide, titanium oxide and Prussian - 7o — Blue, and c dyes such as alizarin dyes, azo dyes and metal phthalocyanine dyes, and nutrients and trace nutrients such as salts of iron, ese, boron, copper, cobalt, molybdenum and zinc.
Additional components may be stabilizers, such as cold stabilizers, preservatives, antioxidants, light stabilizers, or other agents which improve chemical and/or physical stability. Foam generators or antifoams may also be present.
In addition, the formulations and the use forms derived therefrom may also se, as additional auxiliaries, stickers such as carboxymethyl cellulose and natural and synthetic polymers in the form of powders, granules or latices, such as gum arabic, polyvinyl l and polyvinyl acetate, or else l phospholipids such as cephalins and ins and synthetic olipids. Further possible auxiliaries are mineral and vegetable oils.
Optionally, further auxiliaries may be present in the formulations and the use forms derived therefrom. es of such additives include fragrances, protective colloids, binders, adhesives, thickeners, thixotropic agents, penetrants, retention promoters, stabilizers, sequestrants, complexing agents, humectants, Spreaders. In general, the compounds of the formula (I) can be combined with any solid or liquid additive ly used for ation purposes.
Useful retention promoters e all those substances which reduce the c surface tension, for example dioctyl sulphosuccinate, or increase the Viscoelasticity, for example hydroxypropylguar polymers.
Useful penetrants in the present context are all those substances which are typically used to improve the penetration of active agrochemical ingredients into plants. Penetrants are defined in this context by their ability to penetrate from the (generally s) application liquor and/or from the the mobility of active ingredients in the spray coating into the cuticle of the plant and thereby increase cuticle. The method described in the literature (Baur et al., 1997, Pesticide Science 51, 131-152) can be used for determining this property. Examples include alcohol alkoxylates such as coconut fatty ethoxylate (10) or isotridecyl ethoxylate (12), fatty acid esters, for example ed oil methyl ester or ammonium soya oil methyl ester, fatty amine alkoxylates, for example tallowamine ethoxylate (15), or and/or onium salts, for example ammonium sulphate or diammonium hydrogenphosphate.
The ations preferably contain between 0.00000001% and 98% by weight of the compound of the formula (I), more preferably between 0.01% and 95% by weight of the compound of the formula (I), most ably between 0.5% and 90% by weight of the compound of the formula (I), based on the weight of the formulation.
The content of the compound of the a (I) in the use forms prepared from the formulations (especially pesticides) may vary within wide ranges. The concentration of the compound of the formula (I) in the use forms may typically be between 0.00000001% and 95% by weight of the compound of the ‘ » 77 — formula (1), ably between 1% and 1% by weight, based on the weight of the use form.
Application is lished in a customary manner appropriate for the use forms.
The compounds of the formula (I) can also be used in a mixture with one or more suitable fungicides, bactericides, acaricides, molluscicides, nematicides, icides, microbiologicals, beneficial organisms, herbicides, izers, bird repellents, phytotonics, sterilants, safeners, semiochemicals and/or plant growth regulators, in order thus, for example, to broaden the spectrum of , to prolong the duration of action, to increase the rate of action, to prevent repulsion or prevent evolution of resistance. In addition, active ient combinations of this kind can improve plant growth and/or tolerance to abiotic factors, for example high or low temperatures, to drought or to elevated water content or soil salinity. It is also possible to improve flowering and fruiting performance, optimize ation capacity and root development, facilitate harvesting and improve yields, influence tion, improve the quality and/or the nutritional value of the ted products, g storage life and/or improve the processability of the harvested products.
In addition, the compounds of the formula (I) may be present in a mixture with other active ingredients or semiochemicals such as attractants and/or bird repellents and/or plant activators and/or growth regulators and/or fertilizers. Likewise, the compounds of the formula (I) can be used in mixtures with agents to improve plant properties, for example growth, yield and quality of the harvested material.
In a particular embodiment of the invention, the compounds of the formula (I) are in the form of formulations or the use forms prepared from these formulations in a mixture with further compounds, preferably those as described below.
If one of the compounds mentioned below can occur in various tautomeric forms, these forms are also included even if not itly mentioned in each case.
Insecticides/nonricitles/nenmticides The active ingredients specified here with their n names" are known and are described for example in The Pesticide Manual, 16th ed., British Crop Protection Council 2012, or can be searched for on the Internet (6. g. http://www.alanwood.net/pesticides). (1) Acetylcholinesterase (AChE) inhibitors, for example carbamates, e.g. alanycarb, rb, carb, benfuracarb, butocarboxim, butoxycarboxim, carbaryl, carbofuran, carbosulfan, ethiofencarb, fenobucarb, formetanate, furathiocarb, isoprocarb, methiocarb, methomyl, metolcarb, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, trimethacarb, XMC and xylylcarb; or organophosphates, e.g. acephate, hiphos, azinphos-ethyl, azinphos- methyl, cadusafos, chlorethoxyfos, envinphos, chlormephos, yrifos, chlorpyrifos- methyl, hos, cyanophos, demeton—S-methyl, diazinon, dichlorvos/DDVP, dicrotophos, dimethoate, dimethylvinphos, disulfoton, EPN, ethion, ethoprophos, famphur, fenamiphos, ‘ — 78 - fenitrothion, fenthion, azate, heptenophos, fos, isofenphos, isopropyl O— (methoxyaminothiophosphoryl) salicylate, isoxathion, malathion, mecarbam, methamidophos, methidathion, mevinphos, monocrotophos, naled, omethoate, oxydemeton—methyl, parathion, parathion-methyl, phenthoate, phorate, phosalone, phosmet, phosphamidon, phoxim, pirimiphos- methyl, profenofos, propetamphos, prothiofos, pyraclofos, pyridaphenthion, quinalphos, sulfotep, tebupirimfos, temephos, terbufos, tetrachlorvinphos, thiometon, triazophos, rfon and vamidothion. (2) GABA-gated chloride l antagonists, for example cyclodiene-organo’chlorines, e.g. chlordane and endosulfan or phenylpyrazoles (fiproles), e.g. ethiprole and fipronil. (3) Sodium channel modulators/voltage-gated sodium charmel blockers, for example pyrethroids, e.g. acrinathrin, allethrin, d—cis-trans allethrin, d-trans allethrin, bifenthrin, bioallethrin, bioallethrin s- cyclopentenyl isomer, bioresmethrin, cycloprothrin, rin, beta—cyfluthrin, cyhalothrin, lambda-cyhalothrin, gamma-cyhalothrin, cypermethrin, alpha—cypermethrin, beta-cypermethrin, cypermethrin, ypermethrin, cyphenothrin [(1R)-trans isomer], deltamethrin, empenthrin [(EZ)—(lR) isomer], esfenvalerate, prox, fenpropathrin, fenvalerate, flucythrinate, flumethrin, tau-fluvalinate, prox, imiprothrin, kadethrin, permethrin, phenothrin [(1R)-trans isomer], prallethrin, rins (pyrethrum), resmethrin, silafluofen, tefluthrin, tetramethrin, tetramethrin [(lR) isomer)], tralomethrin and transfluthrin or DDT or methoxychlor. (4) Nicotinergic acetylcholine receptor (nAChR) agonists, for example neonicotinoids, e.g. acetamiprid, clothiam'din, dinotefuran, imidacloprid, nitenpyram, thiacloprid and thiamethoxam or nicotine or sulfoxaflor. (5) Allosteric tors of the nicotinergic acetylcholine receptor ), for example spinosyns, e.g. spinetoram and spinosad. (6) Chloride channel activators, for example, ctins/milbemycins, e.g. abamectin, emamectin benzoate, lepimectin and ectin. (7) Juvenile hormone imitators, for example, juvenile hormone ues e.g. hydroprene, kinoprene and methoprene or fenoxycarb or pyriproxyfen. (8) Active ients with unknown or cific mechanisms of action, for example alkyl halides, e.g. methyl e and other alkyl halides; or chloropicrine or sulphuryl fluoride or borax or tartar emetic. (9) Selective antifeedants, e. g. pymetrozine or flonicamid.
W0 2015/067647 — 79 - (10) Mite growth inhibitors, e. g. clofentezine, hexythiazox and diflovidazin or etoxazole. (11) Microbial disruptors of the insect gut membrane, e.g. Bacillus thuringiensis subspecies israelensis, Bacillus sphaericus, us thuringiensis subspecies aizawai, Bacillus thuringiensis subspecies kurstaki, Bacillus thuringiensis subspecies tenebrionis, and BT plant proteins: CrylAb, CrylAc, CrylFa, CryZAb, mCry3A, Cry3Ab, Cry3Bb, Cry34/35Abl. (12) Oxidative phosphorylation inhibitors, ATP disruptors, for example diafenthiuron or tin compounds, e.g. azocyclotin, cyhexatin and fenbutatin oxide or propargite or tetradifon. (13) Oxidative phosphorylation lers that interrupt the H proton gradient, for e chlorfenapyr, DNOC and sulfluramid. (14) Nicotinergic choline receptor antagonists, for example tap, cartap hydrochloride, thiocyclam, and ltap—sodium. (15) Chitin biosynthesis tors, type 0, for example bistrifluron, chlorfluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, muron, teflubenzuron and triflumuron. (16) Chitin biosynthesis inhibitors, type 1, for example buprofezin. (17) Moulting inhibitors (especially for Diptera, i.e. dipterans), for e cyromazine. (18) Ecdysone receptor agonists, for example chromafenozide, halofenozide, methoxyfenozide and tebufenozide. (19) Octopaminergic agonists, for example z. (20) Complex-III electron transport inhibitors, for example hydramethylnon; or acequinocyl; or fluacrypyrim. (21) Complex—I electron transport inhibitors, for example from the group of the METI acaricides, e.g. fenazaquin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad and pyrad or rotenone (Derris). (22) Voltage-gated sodium channel blockers, for example indoxacarb or metaflumizone. (23) Inhibitors of acetyl-CoA carboxylase, for example tetronic and ic acid derivatives, e.g. spirodiclofen, spiromesifen and spirotetramat. - 8O — (24) Complex-IV on transport inhibitors, for example phosphines, e.g. aluminium phosphide, calcium phosphide, phosphine and zinc phosphide or cyanide. (25) Complex—II electron transport inhibitors, for example cyenopyrafen and cyflumetofen. (28) Ryanodine or ors, for example es, e.g. chlorantraniliprole, cyantraniliprole and flubendiamide, further active ingredients, for example afidopyropen, azadirachtin, benclothiaz, benzoximate, bifenazate, bromopropylate, chinomethionat, te, dicofol, diflovidazin, fluensulfone, flometoquin, flufenerim, flufenoxystrobin, flufiprole, am, flupyradifurone, filfenozide, heptafluthrin, imidaclothiz, iprodione, meperfluthrin, ngding, pyflubumide, pyrifluquinazon, pyriminostrobin, ethylfluthrin and iodomethane; and also preparations based on Bacillus firmus 2, BioNeem, Votive), and also the ing compounds: 3- bromo—N— {2-bromochlor0[(l -cyclopropylethyl)carbamoyl]phenyl} —l -(3 -chloropyridinyl)-1H- pyrazole-S -carboxamide (known from W02005/077934) and l-{2-fluoromethyl-5—[(2,2,2- trifluoroethyl)sulphinyl]phenyl}-‘3 -(trifluoromethyl)-lH-l ,2,4-triazole-5 —amine (known from W02006/043635), {l‘-[(2E)-3 -(4-chlorophenyl)prop-2—en-l —yl] —5-fluorospiro[indole-3 ,4'—piperidin]— l(2H)-yl}(2-chloropyridin—4-yl)methanone (known from W02003/106457), 2—chloro—N—[2-{1-[(2E) (4-chlorophenyl)propen-l-yl]piperidin—4-yl}(trifluoromethyl)phenyl]isonicotinamide (known from /003494), 3-(2,5—dimethylphenyl)hydroxymethoxy—l ,8-diazaspiro[4.5]dec—3 one (known from W02009/049851), 3-(2,5-dimethylphenyl)methoxy-2—oxo-1,8-diazaspiro[4.5]decen- 4-yl-ethylcarbonate (known from W02009/049851), 4—(but-2—yn-l-yloxy)(3,5-dimethylpiperidin—l- yl)flu0ropyrimidine (known from W02004/099160), 4—(butyn-1 -yloxy)(3- chlorophenyl)pyrimidine (known from W02003/076415), PF1364 (CAS Reg. No. 12047762), 4-[5- (3 ,5—dichlorophenyl)—5-(trifluoromethyl)—4,5 -dihydro-1 ,2-oxazol—3-yl]methyl-N— {2-oxo-2—[(2,2,2- trifluoroethyl)amino]ethyl}benzamide (known from W02005/085216), 4-{5-[3 -chloro (trifluoromethyl)pheny1](triflu0romethyl)~4,5 -dihydro-l ,2—oxazol—3-yl} -N- —2-[(2,2,2— trifluoroethyl)amino]ethyl}-l -naphthamide (known from W02009/002809), methyl 2-[2-({[3-bromo-l- (3 -chloropyridinyl)- lH-pyrazol-S -y1]carbonyl} amino)-5~chloro~3—methylbenzoyl] -2 - methylhydrazinecarboxylate (known from W02005/085216), methyl 2—[2-({[3-bromo-l-(3- chloropyridinyl)- 1H—pyrazol-S -yl]carbonyl} amino)cyano-3 —methylbenzoyl] -2— ethylhydrazinecarboxylate (known from W02005/085216), methyl 2-[2-({[3-bromo—l -(3—chloropyridin— 2—yl)- lH—pyrazol—S-y1]carbonyl} amino)-5 -cyano—3 —methylbenzoyl] —2—methylhydrazinecarboxylate (known from W02005/085216), methyl 2—[3,5-dibromo-2—({[3-brom0-l-(3~chloropyridin—2-yl)—1H- pyrazol-S-yl]carbonyl}amino)benzoyl]ethylhydrazinecarboxylate (known from W02005/085216), l- (3 opyridinyl)—N—[4—cyanomethyl(methylcarbamoyl)phenyl]-3 - {[5—(trifluoromethyl)—2H— tetrazol-Z-yl]methyl}-1H—pyrazole—5 —carboxamide (known from W02010/069502), N—[2-(5 -amino- 1,3 ,4—thiadiazolyl)chloro—6-methylphenyl] -3 —bromo—1 -(3 -chloropyridin-2—yl)-1H-pyrazole—5 - carboxamide (known from CN102057925), 3-chloro-N-(2-cyanopropan-2—y1)-N—[4—(1,1,1,2,3,3,3- heptafluoropropan—2—yl)methylpheny1]phthalamide (known from W02012/034472), 8-chloro-N-[(2- chloro-S-methoxypheny1)sulphonyl](trifluoromethyl)imidazo[1,2-a]pyridinecarboxamide (known from W02010/129500), 4—[5-(3,5-dichlorophenyl)—5-(trifluoromethyl)—4,5-dihydro-1,2-oxazolyl] methyl-N—(l-oxidothietan—3-yl)benzamide (known from WO2009/080250), 4-[5-(3,5-dichlorophenyl) (trifluOromethyl)—4,5 —dihydro-1 ,2-oxazol-3 -y1] methyl-N-(1 -oxidothietanyl)benzamide (known from W02012/029672), 1-[(2-chloro-1,3-thiazol-5—yl)methyl]—4-oxophenyl-4H—pyrido[1,2— a]pyrimidin—1-ium—2-olate (known from W02009/099929), 1-[(6-chloropyridin—3-y1)methyl]—4-oxo—3- pheny1-4H- [1 ,2-a]pyrimidiniumolate (known from /099929), (5 S,8R)[(6-chloropyridin-3 - yl)methyl] ro—2,3 ,5,6,7, hydro-1H-5 , 8-epoxyimidazo[1,2-a]azepine (known from W02010/069266), (2E)[(6-chloropyridinyl)methy1]-N'~nitro-2— pentylidenehydrazinecarboximidamide (known from W020 10/0602-3 1), 4-(3- {2,6-dichloro[(3 ,3- dichloroprop-Z-en-l -yl)oxy]phenoxy}propoxy)—2-methoxy(trifluoromethyl)pyrimidine (known from CN101 3 37940), N—[2-(teIt-butylcarbamoyl)chloro-6—methylpheny1]-1 -(3 -chloropyridinyl)-3 - (fluoromethoxy)—1H—pyrazole—S-carboxamide (known from W02008/134969).
Fungicides The active ingredients specified herein by their common name are known and described, for example, in the "Pesticide Manua " or on the Internet (for example: http://www.alanwoodnet/pesticides). (1) Ergosterol biosynthesis inhibitors, for example (1.1) aldimorph, (1.2) azaconazole, (1.3) bitertanol, (1.4) bromuconazole, (1.5) cyproconazole, (1.6) diclobutrazole, (1.7) difenoconazole, (1.8) diniconazole, (1.9) diniconazole—M, (1.10) dodemorph, (1.11) dodemorph e, (1.12) onazole, (1.13) etaconazole, (1.14) fenarimol, (1.15) fenbuconazole, (1.16) fenhexamid, (1.17) fenpropidin, (1.18) fenpropimorph, (1.19) fluquinconazole, (1.20) midol, (1.21) flusilazole, (1.22) flutriafole, (1.23) furconazole, (1.24) furconazole-cis, (1.25) nazole, (1.26) imazalil, (1.27) imazalil sulphate, (1.28) imibenconazole, (1.29) zole, (1.30) metconazole, (1.31) myclobutanil, (1.32) naftifin, (1.33) nuarimol, (1.34) oxpoconazole, (1.35) paclobutrazole, (1.36) pefurazoate, (1.37) penconazole, (1.38) piperalin, (1.39) prochloraz, (1.40) propiconazole, (1.41) oconazole, (1.42) pyributicarb, (1.43) pyrifenox, (1.44) quinconazole, (1.45) simeconazole, (1.46) spiroxamine, (1.47) nazole, (1.48) terbinafin, (1.49) tetraconazole, (1.50) triadimefon, (1.51) triadimenol, (1.52) tridemorph, (1.53) triflumizole, (1.54) triforine, (1.55) triticonazole, (1.56) uniconazole, (1.57) azole-P, (1.58) Viniconazole, (1.59) voriconazole, (1.60) 1—(4-chlorophenyl)(1H-1,2,4-triazolyl)cycloheptanol, (1.61) methyl l-(2,2-dimethyl-2,3—dihydro—1H—inden-1—yl)-1H—imidazole-S-carboxylate, (1.62) N'-{5— (difluoromethyl)—2-methyl-4—[3 -(trimethylsilyl)propoxy]phenyl} -N-ethyl-N—methylimidoformamide, (1 .63) N—ethyl-N—methyl—N‘- {2-methy1—5 -(trifluoromethy1)-4—[3- thylsilyl)propoxy]phenyl}imidoformamide and (1.64) O-[1—(4—methoxyphenoxy)-3,3— dimethylbutan-Z-yl]-1H—imidazolecarbothioate, (1.65) pyrisoxazole. (2) Respiration inhibitors (respiratory chain inhibitors), for e (2.1) bixafen, (2.2) boscalid, (2.3) carboxin, (2.4) diflumeton'm, (2.5) am, (2.6) am, (2.7) flutolanil, (2.8) fluxapyroxad, (2.9) furametpyr, (2.10) funnecyclox, (2.11) azam mixture of the syn-epimeric racemate 1RS,4SR,9RS and the anti-empimeric racemate 1RS,4SR,9SR, (2.12) azam (anti-epimeric racemate), (2.13) azam (anti-epimeric enantiomer 1R,4S,9S), (2.14) isopyrazam (anti—epimeric enantiomer 1S,4R,9R), (2.15) isopyrazam (syn-epimeric racemate 1RS,4SR,9RS), (2.16) isopyrazam pimeric enantiomer 1R,4S,9R), (2.17) isopyrazam (syn—epimeric enantiomer IS,4R,9S), (2.18) il, (2.19) oxycarboxin, (2.20) penflufen, (2.21) penthiopyrad, (2.22) sedaxane, (2.23) thifluzamide, (2.24) 1— methyl-N—[2-(1 ,1 ,2,2-tetrafluoroethoxy)pheny1]-3 uoromethyl)-1H—pyrazole—4-carboxamide, (2.25) uoromethyl)—1 -methy1—N—[2—(1 ,1 ,2,2-tetrafluoroethoxy)pheny1]-1H—pyrazolecarboxamide, (2.26) 3 —(difluoromethyl)~N—[4-fluoro(1 ,1 ,2,3,3 ,3-hexafluoropropoxy)phenyl]methyl-1H—pyrazole— 4-carboxamide, (2.27) N—[1 -(2,4-dichlorophenyl)~1 -methoxypropan—2-yl]-3—(difluoromethy1)- 1 ~methyl— 1H—pyrazole—4-carboxamide, (2.28) 5,8-difluoro-N—[2—(2-fluoro{[4~(trifluoromethy1)pyridin yl]oxy}pheny1)ethy1]quinazolineamine, (2 .29) benzovindiflupyr, (2.30) N—[(1 S,4R) (dichloromethylene)-1 ,2,3,4-tetrahydr0—1,4-methanonaphthalen-5 —y1]-3 -(difluoromethyl)-1 -methy1—1H— pyrazole—4-carboxamide and (2.3 1) N—[(1R,4S)—9—(dich10romethylene)-1 ,2,3 ,4-tetrahydro-1,4- methanonaphthalen—S-y1]-3 -(difluoromethyl)-1 -methyl-1H-pyrazole—4—carboxamide, (2.32) 3- (difluoromethyl)-1 -methyl-N—(1 ,1 ,3—trimethyl-2,3 -dihydro-1H—indeny1)-1H-pyrazolecarboxamide, (2.3 3) 1,3,5 -trimethyl-N—(1 ,1,3-trimethy1—2,3 -dihydro-1H-indeny1)-1H-pyrazole—4-carboxamide, (2.34) 1-methy1—3 -(trifluoromethyl)-N—(1 ,1 ,3-trimethyl—2,3 -dihydro-1H—indeny1)—1H-pyrazole carboxarnide, (2.35) 1-methy1(trifluoromethy1)—N-[(3R)-1,1,3-trimethy1—2,3-dihydro-1H—inden—4-yl]— 1H—pyrazolecarboxamide, (2.36) 1-methy1—3-(trifluorornethy1)-N—[(3S)—1,1,3-trimethy1—2,3-dihydro- 1H—indenyl]-1H—pyrazolecarboxamide, (2.37) 3 —(difluoromethy1)-1 -methy1—N—[(3 S)-1,1,3- trimethyl-2,3-dihydro-1H—inden—4-y1]-1H-pyrazolecarboxamide, (2.38) 3-(difluoromethyl)methy1- N—[(3R)—1 ,1 ,3 -trimethyl-2,3 -dihydro- l H—indenyl] —1H—pyrazolecarboxamide, (2.39) 1 ,3,5- trimethyl—N—[(3R)-1 ,1 ,3 —trimethy1-2,3-dihydro-1H—indeny1]-1H-pyrazolecarboxamide, (2.40) 1 ,3 ,5-trimethyl—N—[(3 S)—1 ,1 ,3-trimethy1—2,3 —dihydro-1H—indeny1]—1H—pyrazolecarboxamide, (2.41) benodanil, (2.42) ro-N-(1 ,1 ,3-trimethy1—2,3—dihydro-1H—inden—4—yl)pyridine-3 -carboxamide, (2.43) isofetamid (3) Respiration inhibitors (respiratory chain inhibitors) that act on complex III of the respiratory chain, for example (3.1) ametoctradin, (3.2) amisulbrom, (3.3) azoxystrobin, (3.4) cyazofamid, (3.5) coumethoxystrobin, (3.6) coumoxystrobin, (3.5) dimoxystrobin, (3.8) enestroburin, (3.9) famoxadone, (3.10) fenamidone, (3.11) xystrobin, (3.12) fluoxastrobin, (3.13) kresoxim—methyl, (3.14) metominostrobin, (3.15) orysastrobin, (3.16) picoxystrobin, (3.17) pyraclostrobin, (3.18) WO 67647 — 83 - pyrametostrobin, (3.19) pyraoxystrobin, (3 .20) ncarb, (3.21) triclopyricarb, (3 .22) trifloxystrobin, (3 .23) (2E)-2—(2- { [6—(3 -chloro—2-methylphenoxy)—5 -fluoropyrimidin—4—yl] oxy} phenyl) (methoxyimino)-N-methylethanamide, (3 .24) (2E)—2-(methoxyimino)-N-methyl-2—(2- { [( {(1 E)-1 - [3 - (trifluoromethyl)phenyl]ethylidene} oxy]methyl}phenyl)ethanamide, (3 .25) (2E) xyimino)-N-methyl—2- {2-[(E)-( { 1 —[3 - (trifluoromethyl)phenyl]ethoxy} imino)methy1]phenyl} ethanamide, (3 .26) (2B)—2- {2- [( { [(1 E)—l -(3 - {[(E)-1 -fluorophenylethenyl]oxy}phenyl)ethylidene]amino} oxy)methyl]phenyl} (methoxyimino)— N—methylethanamide, (3 .27) (2E)—2- {2-[( { [(2E,3E)—4-(2,6—dichlorophenyl)but-3 -en—2- ylidene]amino } oxy)methyl]phenyl} -2~(methoxyimino)-N-methylethanamide, (3 .2 8) 2-chloro-N—(1 , l ,3 - trimethyl—2,3-dihydro-lH—inden—4—yl)pyridinecarb0xamide, (3 .29) 5-methoxy—2—methy1—4-(2- {[( {(1E)-1 -[3 -(trifluoromethyl)phenyl]ethylidene}amino)oxy]methyl}phenyl)—2,4-dihydro-3H-1 ,2,4— triazol—3 -one, (3 .30) methyl (2E) {2—[( {cyclopropyl[(4- methoxyphenyl)imino]methyl} sulphanyl)methyl]phenyl} —3-methoxypropenoate, (3 .3 1) N—(3 -ethyl- 3 ,5,5-trimethylcyclohexyl)(formylamino)-2—hydroxybenzamide, (3 .32) 2— {2-[(2,5— dimethylphenoxy)methyl]phenyl}methoxy-N—methylacetamide, (4) tors of mitosis and cell division, for example (4.1) benomyl, (4.2) carbendazim, (4.3) chlorfenazole, (4.4) diethofencarb, (4.5) ethaboxam, (4.6) fluopicolid, (4.7) fuberidazole, (4.8) pencycuron, (4.9) thiabendazole, (4.10) thiophanate-methyl, (4.11) thiophanate, (4.12) zoxamide, (4.13) 5-chloro~7—(4-methylpiperidinyl) (2,4,6-trifluorophenyl)[l,2,4]triazolo[l,5-a]pyrimidine and (4.14) 3-chloro-5~(6-chloropyridin—3-yl) methyl-4—(2,4,6-trifluorophenyl)pyridazine. (5) Compounds having multisite activity, for example (5.1) Bordeaux mixture, (5.2) captafol, (5.3) captan, (5.4) chlorothalonil, (5.5) copper ations such as copper hydroxide, (5.6) copper naphthenate, (5.7) copper oxide, (5.8) copper oxychloride, (5.9) copper sulphate, (5.10) dichlofluanid, (5.11) dithianon, (5.12) dodine, (5.13) dodine free base, (5.14) ferbam, (5.15) fluorfolpet, (5.16) folpet, (5.17) guazatine, (5.18) guazatine acetate, (5.19) iminoctadine, (5.20) iminoctadine albesilate, (5.21) iminoctadine triacetate, (5.22) mancopper, (5.23) eb, (5.24) maneb, (5.25) metiram, (5.26) zinc metiram, (5.27) copper-oxine, (5.28) propamidine, (5.29) propineb, (5.30) sulphur and sulphur preparations, for e m lphide, (5.31) , (5.32) tolylfluanid, (5.33) zineb, (5.34) ziram and (5.35) anilazine. (6) Resistance inducers, for example (6.1) acibenzolar-S-methyl, (6.2) isotianil, (6.3) probenazole, (6.4) tiadinil and (6.5) laminarin. (7) Amino acid and protein biosynthesis tors, for example (7.1), (7.2) blasticidin—S, (7.3) cyprodinil, (7.4) kasugamycin, (7.5) kasugamycin hydrochloride hydrate, (7.6) mepanipyrim, (7.7) pyrimethanil, (7.8) 3—(5-fluoro-3,3,4,4-tetramethyl-3,4-dihydroisoquinolinyl)quinoline and (7.9) oxytetracycline and (7.10) streptomycin. — 84 - (8) ATP production inhibitors, for example (8.1) fentin acetate, (8.2) fentin chloride, (8.3) fentin hydroxide and (8.4) silthiofam. (9) Cell wall synthesis inhibitors, for example (9.1) benthiavalicarb, (9.2) dimethomorph, (9.3) flumorph, (9.4) licarb, (9.5) mandipropamid, (9.6) polyoxins, (9.7) polyoxorim, (9.8) validamycin A, (9.9) valifenalate and (9.10) polyoxin B. (10) Lipid and membrane synthesis inhibitors, for example (10.1) biphenyl, (10.2) chlorneb, (10.3) dicloran, (10.4) phos, (10.5) etridiazole, (10.6) iodocarb, (10.7) nfos, (10.8) isoprothiolane, (10.9) propamocarb, (10.10) ocarb hydrochloride, (10.11) prothiocarb, (10.12) pyrazophos, (10.13) quintozene, ) tecnazene and (10.15) tolclofos-methyl. (11) Melanin biosynthesis inhibitors, for example (11.1) carpropamid, (11.2) diclocymet, (11.3) fenoxanil, (11.4) fthalide, (11.5) pyroquilon, (11.6) tricyclazole and (11.7) 2,2,2—trifluoroethyl {3- -l -[(4-methylbenzoyl)amino]butanyl} carbamate. (12) Nucleic acid synthesis tors, for e (12.1) benalaxyl, (12.2) benalaxyl-M axyl), (12.3) bupirimate, (12.4) clozylacon, (12.5) dimethirimol, (12.6) ethirimol, (12.7) furalaxyl, (12.8) hymexazole, (12.9) metalaxyl, (12.10) metalaxyl—M (mefenoxam), ) ofurace, (12.12) oxadixyl, (12.13) oxolinic acid and (12.14) inone. (13) Signal transduction tors, for example (13.1) chlozolinate, (13.2) lonil, (13.3) fludioxonil, (13.4) iprodione, (13.5) procymidone, (13.6) quinoxyfen, (13.7) Vinclozolin and (13.8) proquinazid. (14) Decouplers, for example (14.1) binapacryl, (14.2) dinocap, (14.3) ferimzone, (14.4) fluazinam and (14.5) meptyldinocap. (15) Further compounds, for example (1 5.1) benthiazole, (15.2) bethoxazine, (15.3) capsimycin, (15.4) .8) cyflufenamid, carvone, (1 5 .5) chinomethionat, (15 .6) pyriofenone (chlazafenone), (1 5 .7) cufraneb, (1 (15.9) cymoxanil, ) cyprosulfamide, (15.1 1) dazomet, (15.12) debacarb, (15.13) dichlorophen, (1 5 . 1 4) diclomezine, (1 5 l 6) difenzoquat methylsulphate, (1 5 . 17) diphenylamine, . 1 5) difenzoquat, (1 5. (15.18) EcoMate, (15.19) fenpyrazamine, (15.20) flumetover, (15.21) fluorimid, (15.22) flusulfamide, (15.23) flutiam'l, (15.24) fosetyl-aluminium, ) fosetyl-calcium, (15.26) fosetyl-sodium, (15.27) hexachlorobenzene, (15.28) irumamycin, (1 5 .29) ulfocarb, (1 5 .30) methyl isothiocyanate, (1 5 .3 1) metrafenone, (1 5 .32) mildiomycin, (1 5 .33) natamycin, (l 5 .34) nickel dimethyldithiocarbamate, (1 5 .35) nitrothal-isopropyl, (15.36) octhilinone, (15.37) oxamocarb, (15.3 8) oxyfenthiin, (l 5.39) pentachlorophenol and its salts, (15.40) phenothn'n, ) phosphoric acid and its salts, (15.42) propamocarb—fosetylate, (15.43) propanosine-sodium, (15.44) pyrimorph, ) (2E)(4-tert- butylphenyl)-3 -(2-chloropyridin—4—yl)—1 -(morpholin—4—yl)prop-2—en—1 —one, (1 5 .46) (2Z)-3 -(4-tert~ butylphenyl)-3—(2-chloropyridin—4-yl)-1 -(morpholin—4-yl)prop—2-en-1 -one, (1 5 .47) pyrrolnitrin, (1 5 .4 8) ‘ — 85 - tebufloquin, ) tecloftalam, (15.50) tolnifanide, (15.51) triazoxide, (15 .52) trichlamide, ) zarilamid, (15.54) (3 R,8R)—8 -benzy1—3 -[( {3-[(isobutyry10xy)meth0xy] -4—methoxypyridin—2- y1} y1)amino] —6-1nethy1-4,9-dioxo—1 ,5 -dioxonan—7-y1 2-methylpr0panoate, (15.55) 1-(4- {4-[(5R)-5 - (2,6-diflu0rophenyl)-4,5-dihydro-1 ,2—oxazol—3 -y1]—1,3 -thiazo1y1}piperidin—1 -y1)—2-[5-methy1 (trifluoromethyl)—1H-pyraz01—1—y1]ethan0ne, (1 5 .56) 1-(4- {4-[(5S)(2,6-difluor0pheny1)—4,5-dihydI0-1 ,2- 0xaz01—3-y1] - 1 ,3 -thiazoly1}piperidin—1-y1)—2-[5-methy1-3 uoromethy1)-1H—pyraz01-1 -y1]ethanone, (15.57) 1-(4-{4-[5-(2,6-difluoropheny1)—4,5-dihydr0—1,2—oxazol-3 -y1]-1,3—thiazoly1}piperidin—1-y1) [5-methy1~3-(trifluoromethyl)—1H—pyrazoly1]ethanone, (15.58) 1-(4-methoxyphenoxy)-3 ,3 - dimethylbutan-Z-yl 1H—imidazole-1 -carb0xy1ate, (1 5.59) 2,3 ,5,6-tetrachloro(methy1su1phony1)pyfidine, (15.60) 2,3-dibuty1ch10rothieno[2,3-d]pyrimidin—4(3H)-one, (15.61) methy1—1H,5H— [1 ,4]dithiino[2,3-c:5 ,6-c']dipyrrole-1 ,3,5,7(2H,6H)-tetrone, (15.62) 2—[5-methy1—3—(trifluoromethy1)—1H- pyraz01-1 -y1](4-{4-[(5R)pheny1-4,5 —dihydro—1 ,2-0xaz01y1] -1 ,3-thiazoly1}piperidin—1 - y1)ethanone, (15.63) 2—[5-methy1—3 -(trifluoromethy1)-1H—pyrazol-l -y1]-1 -(4- {4-[(5 S)pheny1—4,5 - dihydro—l,2-0xazol—3—y1]—1,3-thiaz01y1}piperidin—l —y1)ethanone, (15.64) 2-[5 -methy1—3— (trifluoromethyl)-1H-pyrazol-1 -y1] —1 - {4-[4-(5~phenyl-4,5-dihydro—1,2-0xazol-3 —y1)-1 ,3-thiazol—2- y1]piperidin—1-y1}ethanone, (1 5 .65) 2—but0xy—6-iod0propy1—4H—chr0menone, (15.66) 2jch10ro[2- chloro-l -(2,6-difluor0-4—methoxypheny1)methyl— 1 H-imidazol-S-y1]pyridine, (1 5 .67) 2-pheny1phen01 and salts, (15.68) ,5 -trifluor0-3,3-dimethy1—3,4—dihydrois0quinolin—1-y1)quinoline, (15.69) 3,4,5- trichloropyridine-Z,6-dicarbonitrile, (15.70) 3-ch10r0—5-(4-ch10rophenyl)-4—(2,6-diflu0r0pheny1)—6- methylpyridazine, (1 5 .7 1) 4-(4-ch10ropheny1)—5 -(2,6-difluoropheny1)-3,6-dimethy1pyridazine, (1 5 .72) 5 - 1 ,3 ,4-thiadiazolethi01, (15.73) 5 -ch10ro-N‘—pheny1-N'-(pr0pyny1)thiophene sulphonohydrazide, (1 5 .74) 5—fluoro[(4-fluorobenzy1)oxy]pyrimidine-4—amjne, (1 5 .75) 5 -fluoro—2-[(4— methylbenzyl)oxy]pyrimidine-4—amine, (1 5 .76) 5-methyl-6—octy1[1 ,2,4]triazolo [1 ,5-a]pym'midineamine, (15.77) ethyl (2Z)aminocyanopheny1acry1ate, (15.78) N‘-(4- {[3 -(4-chlor0benzy1)-1 ,2,4-thiadiazol- 5 -y1]oxy} -2,5-dimethy1pheny1)-N—ethy1-N-methylimidof0rmamide, (1 5 .79) N—(4-chlorobenzy1)-3 -[3 — methoxy-4—(propyn-1 —y1oxy)pheny1]pr0panamide, (15 .80) N-[(4-ch10ropheny1)(cyano)methy1]-3 -[3 - methoxy—4—(pr0p—2-yn— 1 -y10xy)pheny1]propanamide, (1 5 .8 1) bromo-3 -ch10r0pyridin—2-yl)methy1]— 2,4-dichloronicotinamide, (1 5 .82) N-[1 -(5-br0moch10r0pyridin—2-y1)ethy1]-2,4—dich10ronicotinamide, (15.83) N—[1-(5-bromo-3—ch10ropyridin—2-yl)ethy1]flu0r0iodonicotinamide, (15.84) N— {(E)- [(cyclopropylmethoxy)imino] [6-(difluoromethoxy)-2,3-diflu0r0phenyl]methy1} -2—pheny1acetamide, (1 5.8 5) N— (cyclopropy1methoxy)imino][6—(difluoromethoxy)—2,3—difluoropheny1]methyl} phenylacetamide, (1 5 .86) N'— {4-[(3 buty1-4—cyano—1 ,2-thiaz01y1)oxy] ch10r0methylpheny1} -N— ethyl-N-methylimidoformamide, (1 5.87) yl-Z-(l - { [5~methy1—3-(triflu0romethyl)-1H-pyrazoI-1 - yl] acety1}piperidin—4-y1)-N—(1 -tetrahydronaphthaleny1)-1 ,3-thiazole—4—carb0xamide, (15.8 8) N- methy1—2-(1 - { [5-methy1—3-(trifluoromethy1)—1H-pyrazoly1]acety1}piperidinyl)~N—[(1R)—1 ,2,3 ,4— tetrahydronaphthaleny1] —1 ,3-thiazole-4—carboxamide, (1 5.8 9) N—methy1(1 - {[5-methy1—3 — (trifluoromethyl)-1H—pyrazol—l -y1]acetyl}piperidin—4-y1)-N—[(1 S)-1,2,3,4-tetrahydr0naphthalen-1 -y1] -1 ,3 - thiazole—4—carb0xamide, (15.90) pentyl {6-[({[(1—methy1-1H-tetrazol-5 - VVO 2015/067647 - 86 — 2014/073795 yl)(pheny1)methylene]amino} 0xy)methy1]pyridiny1} carbamate, (1 5 .9 1) phenazine-l —carb0xy1ic acid, (15.92) quinolin—8-01, (15.93) quinolin-8—01 sulphate (2: 1), (15 .94) tert-butyl [(1-methy1—1H—tetrazol- —y1)(pheny1)methylene] amino} oxy)methy1]pyn'din-2~y1} carbamate, (1 5 .95) 1 -methy1-3 —(trifluoromethy1)- (trifluoromethyl)bipheny1yl] -1H—pyrazolecarb0xamide, (15.96) N-(4'-ch10robipheny1yl) (difluoromethy1)-1 -methy1-1H-pyrazolecarboxamide, (15.97) N—(2',4'—dich10robiphenyly1) (difluoromethy1)methy1-1H—pyrazolecarboxamide, ) 3-(difluoromethy1)-1—methy1-N—[4'— (trifluoromethy1)biphenyly1]-1H—pyrazolecarboxamide, (15.99) 5'-diflu0robipheny1—2-yl)-1 - methyl—3 -(trifluoromethy1)—1H—pyrazole—4—carb0xamide, (15.100) 3-(difluor0methy1)—1-methy1-N—[4'- (prop-1 -yn-1 -y1)bipheny1y1]-1H—pyrazolecarboxamide, (15.101) 5—fluoro-1,3—dimethy1-N-[4'—(prop— 1 —yn-1 -y1)bipheny1—2—y1]—1H—pyrazole-4—carboxamide, (1 5. 102) 2-chloro-N—[4'—(prop-1 -yn-1 -y1)bipheny1— 2-y1]nicotinamide, (1 5 3 -dimethy1but-1 -yn-1 -y1)bipheny1—2-y1]—1 -methy1— . 103) 3—(difluoromethy1)-N— [4'-(3 , 1H-pyrazole-4—carboxamide, (15.104) N—[4'-(3,3 —dimethy1butyn-1 ~y1)bipheny1—2-y1]fluoro-1 ,3- dimethy1-1 H—pyrazole—4-carboxamide, (1 5 . 1 05) uor0methy1)-N—(4'-ethyny1biphenyly1)-1 1- 1H—pyrazolecarboxamide, (15.106) N—(4'-ethyny1bipheny1—2-y1)-5 -fluoro-1,3-dimethy1-1H—pyrazole carboxamide, (15. 107) 2-ch10ro—N-(4'-ethyny1bipheny1—2-y1)nicotinamide, (15.108) 2-chloro-N-[4'—(3 ,3- d i methyl but—1 -yny1)biphenyl-2—y1]nicotinamide, (1 5 . 1 09) 4-(difluoromethy1)methy1—N—[4'— oromethy1)bipheny1y1]-1,3—thiazole-5 ~carboxamide, (1 5.1 10) 5-flu0r0—N—[4'—(3-hydroxy-3 - methylbut-l -yn—1—y1)bipheny1yl]—1,3-dimethy1-1H—pyrazolecarboxamide, (15. 1 1 1) 2-ch10ro-N—'[4'-(3- hydroxymethy1but-1 -yn-1 —y1)bipheny1—2-y1]nicotinamide, (1 5.1 12) uor0methy1)-N—[4'-(3 - methoxy—3-methy1but-1 -yny1)bipheny1—2-y1] -1 -methy1-1 H—pyrazole-4—carboxamide, (1 5 . 1 1 3) 5—fluoro- N-[4'-(3—methoxymethy1but—1-yny1)biphenyl-2—y1]—1 ,3-dimethy1—1H—pyrazolecarboxamide, (1 5. 1 1 4) ro—N—[4'-(3 -methoxy—3 -methy1but-1 -yn-1 -y1)bipheny1y1]nicotinamide, (1 5 - . 1 1 5) (5 bromo-2—methoxy—4—methy1pyridin—3 -y1)(2,3,4-trimethoxy—6—methylphenyl)methanone, (15.1 1 6) N-[2-(4— {[3-(4-chloropheny1)prop—2-yn—1 -y1]oxy} -3—methoxypheny1)ethy1]-N2-(methy1sulphonyl)va1inamide, (1 5 .1 17) 4—ox0[(2-phenylethy1)amino]butanoic acid, (15.1 1 8) butyn—1-y1 {6-[({[(Z)-(1—methyl-1H— tetrazol-S-y1)(pheny1)methylene]amino} thy1]pyridin—2-y1}carbamate, (1 5 .1 1 9) 4-amino-5 - fluoropyrimidin-Z-ol (tautomeric form: 4-amjn0fluoropyrimidin—2(1H)-one), (1 5 .120) propyl 3,4,5 - trihydroxybenzoate, (15.121) 1,3 -dimethy1—N—(1 ,1 methy1—2,3 —dihydro-1H-inden—4-y1)—1H-pyrazole—4- carboxamide, (15. 122) 1 ,3-dimethy1—N—[(3R)-1 ,1 ,3-trimethyl-2,3—dihydr0-1H—inden—4-y1]-1H-pyrazole—4- carboxamide, (15.123) 1 ,3-dimethy1-N-[(3 S)-1,1 ,3—trimethy1-2,3 -dihydro—1H—inden-4—y1]~1H-pyrazole—4- carboxamide, (15.124) [3-(4-chlorofluorophenyl)(2,4-difluoropheny1)—1 ,2-oxa201y1](pyridin—3- y1)methanol, (15.125) (S)—[3-(4-ch10rofluoropheny1)-5—(2,4-diflu0ropheny1)-1,2-oxazoly1](pyridin-3 — y1)methan01, (15.126) (R)-[3-(4-chlor0fluoropheny1)-5~(2,4-difluor0pheny1)—1 ,2—oxaz01y1](pyridin-3— y1)methanol, (1 5. 1 27) 2- { [3 -(2-chlorophenyl)-2—(2,4-difluoropheny1)oxiran—2-y1]methyl} -2,4-dihydro-3H- 1 ,2,4-triazole-3 -thione, (1 5 . 1 28) 1 - { [3 -(2-chloropheny1)(2,4-diflu0ropheny1)oxirany1]methyl} ~1H- 1 ,2,4-tn'az01—5-y1 thiocyanate, (1 5. 129) 5-(a11y1sulphany1)-1 - {[3-(2-chloropheny1)—2-(2,4- difluoropheny1)oxiran-2—y1]methyl} -1H—1 ,2,4-triazole, (1 5 . 1 30) 2-[1 -(2,4-dich10ropheny1)—5 -hydroxy- 2,6,6-tfimethy1heptanyl]—2,4—dihydro—3H—1,2,4-triazole-3 e, (15.131) 2- { [rel(2R,3 S)—3 —(2- Vx’O 2015/067647 — 87 - chlorophenyl)-2—(2,4-difluorophenyl)oxiran-Z-y1]methy1} —2,4-di11yd1‘0—3H-1 ,2,4-t1‘iazole-3 ~thione, (1 5 . 1 32) 2- {[rel(2R,3R)-3 -(2~011101‘0pheny1)(2,4-difluorophenyl)0xirany1]methyl} -2,4—dihydro-3H— 1 ,2 ,4- tfiazolethione, (15. 1 3 3) 1— {[rel(2R,3 S)-3 101‘0pheny1)(2,4-difluoropheny1)oxirany1]methy1} - 1H—1,2,4-triaz01-5 -y1 thiocyanate, (15.134) 1- {[rel(2R,3R)(2—ch10ropheny1)(2,4- difluoropheny1)oxirany1]methyl} -1H—1 ,2,4-tn'azol—5-y1 thiocyanate, (1 5 — . 1 3 5) 5 -(a11y1su1phany1)-1 {[rel(2R,3S)—3—(2—chlor0pheny1)(2,4-difluorophenyl)oxiran—2-y1]methyl} -1H—1 ,2,4-triazole, (1 5. 1 36) 5- (a11y1su1phanyl)—1 — { [rel(2R,3R)~3-(2-chlorophenyl)-2—(2,4-difluoropheny1)0xiran—2-y1]methyl} - 1 H— 1 ,2,4- triazole, (15.137) 2-[(ZS,4S ,5 S)(2,4-dich10ropheny1)hydroxy-2,6,6-trimethy1heptan—4-yl] -2,4- dihydro-3H-1,2,4-triazoIe—3 e, (15.13 8) 2-[(2R,4S,5S)—1-(2,4—dichlorophenyl)hydroxy—2,6,6— trimethylheptan—4-yl]-2,4—dihydro-3H-1 riazolethi0ne, (15.139) 2-[(2R,4R,5R)—1 -(2,4- dichlorophenyl)—5-hydr0xy—2,6,6-tfimethy1heptan—4—y1]-2,4-dihydro-3H-1 ,2,4-triazole—3 -thione, (1 5. 140) 2-[(2S,4R,5R)-1 -(2,4—dich10r0pheny1)-5—hydroxy—2,6,6-trimethy1heptan—4—y1]-2,4—dihydro-3H—1 ,2,4- triazole-3 -thione, (1 5.141) 2—[(2S,4S,5R)-1 -(2,4-dichloropheny1)hydroxy-2,6,6-trimethy1heptan—4-y1]- 2,4-dihydro—3H—1,2,4-triazole—3-thione, (15.142) 2-[(2R,4S,5R)(2,4-dich10r0pheny1)hydroxy—2,6,6- trimethylheptan—4-y1]-2,4-dihydro-3H—1,2,4—triazole-3 e, (15.143) 2-[(2R,4R,5 S)(2,4— dichlorophenyl)—5—hydroxy—2,6,6—trimethy1heptan—4-yl] -2,4—dihydro-3H—1 ,2,4-triazole-3 -thione, (1 5 .144) 2- [(2S,4R,5 S)—1-(2,4-dich10r0pheny1)—5-hydroxy—2,6,6-t11'methy1heptan—4—y1]-2,4-dihydr0-3H—1 ,2,4- le-3 -thione, (1 5 . 145) 2-fluoro-6—(trifluoromethy1)-N-(1 ,1 ,3—trimethyl-2,3-dihydro-1H—inden-4— y1)benzamide, (15.146) 2-(6-benzy1pyridiny1)quinazoline, (15. 147) 3~fluoromethoxypheny1)-5 - methy1pyridin—2—y1]quinazoline, (1 5 . 148) 3-(4,4-difluoro-3 ethy1—3 ,4-dihydroisoquinolin—1 - y1)quinoline, (15.149) abscisic acid, (15.150) 3-(difluoromethy1)-N-methoxymethy1—N—[1 -(2,4,6- trichlorophenyl)propan—2—y1]—1H—pyrazolecarboxamide, (1 5 . 1 5 1) N'-[5-br0mo(2,3-dihydro-1H— inden—2-y10xy)~2-methy1pyridin—3 -y1]-N-ethy1—N—methylimidoformamide, (1 5. 1 52) N'- {5-bromo[1 - (3 ,5—diflu0ropheny1)eth0xy] —2—methy1pyridin-3 -y1} -N—ethy1—N—methylimidoformamide, (1 5 . 1 53) N'- {5 - bromo—6-[( 1R)-1 ~(3 ,5 -diflu0r0pheny1)ethoxy] ~2-methylpyn'din-3 -y1} y1—N-methylimid0formamide, (1 5. 1 54) N'- {5 —bromo[(1 S)—1 -(3 uoropheny1)ethoxy] methy1pyridin—3 -y1} -N—ethy1—N— methylimidoformanfide, (1 5 — . 1 5 5) N'- {5 -bromo [(cisisopropylcyclohexy1)oxy]—2—methy1pyridin-3 -y1} N—ethyl-N-methylimidoformamide, (1 5 . 1 56) N'- {5-bromo—6—[(trans-4—isopropylcyclohexy1)0xy] methylpyridin—3 —y1} -N-ethyl-N—methylimidoformamide, (15 . 1 57) N—cyclopropyl(diflu0romethy1)-5 - 3O fluoro-N-(2—isopropy1benzy1)-1 —methy1—1H—pyrazole-4—carb0xamide, (1 5 . 1 5 8) N—cyclopropyl-N—(Z- cyclopropylbenzy1)-3~(diflu0r0methy1)fluor0—1 —methy1-1H—pyrazo1e-4—carboxamide, (1 5 . 1 59) N—(2-tertbutylbenzyl )-N—cyc10propy1(difluoromethy1)—5-fluoro-1 -methy1—1H—pyrazolecarboxamide, (15 . 1 60) N—(5 —ch10roethy1benzy1)-N-cyclopropy1-3 -(difluoromethyl)-5~fluoro-1 -methy1—1 zole carboxamide, (1 5 . 1 6 1) h10roisopropy1benzy1)~N—cyclopr0py1-3 -(difluoromethy1)-5 -flu0r0 methyl-1H—pyrazolecarboxamide, (1 5 - . 1 62) N—cyclopropy1—3 -(difluoromethy1)—N—(2-ethy1—5 enzy1)-5 -1 -methy1-1H-pyrazolecarboxamide, (1 5 . 1 63) N—cyclopropy1-3 —(difluoromethy1)— -flu0r0—N—(5-flu0ro-2—isopropy1benzy1)-1 —methy1-1H-pyrazolecarboxamide, (1 5 . 1 64) N—cyc1op1‘0py1- N—(2-cyclopr0py1—5 —flu0robenzy1)—3-(diflu0r0methyl)-5 -flu0ro—1 —methy1—1H—pyrazole—4-carboxamide, WO 67647 — 88 - (15.165) N—(2-cyclopentyl—5 -fluorobenzyl)-N-cyclopropyl(difluoromethyl)-5 -fluoro-1 -methyl-1H— le-4—carboxamide, (15.166) N—cyclopropyl-B -(difluoromethyl)-5 -fluoro-N—(2-fluoro isopropylbenzyl)-1 -methyl- 1H—pyrazole—4—carboxamide, (15. 1 67) N—cyclopropyl-3 -(difluoromethyl)-N-(2- ethylmethy1benzyl)—5 -flu0ro-1 -methy1-1H—pyrazolecarboxamide, (15.168) N—cyclopropy1-3— (difluoromethyl)—5-fluoro-N—(2-is0pr0pylmethy1benzyl)-l -methy1-1H—pyrazole—4-carboxamide, (15.169) opropyl—N—(2-cyclopropyl—5-methylbenzyl)(difluoromethy1)-5—fluoro-1 -methyl-1H- pyrazolecarboxamide, (15.170) N—(2-tert—butyl-5—methylbenzyl)-N~cyclopropyl(difluoromethyl) fluoro-l -methyl-1H—pyrazolecarboxamide, (1 5 .171) N—[5-chloro-2—(trifluoromethyl)benzyl] -N— cyclopropyl(difluoromethyl)—5-flu0ro-1—methyl-1H—pyrazole-4—carboxamide, (15.172) N—cyclopropyl- 3-(diflu0romethyl)fluoromethyl-N-[5-methyl—2-(trifluoromethyl)benzyl]—1H—pyrazole-4— amide, (15.173) N—[2—chloro(trifluoromethy1)benzyl]-N-cyclopropyl—3-(difluoromethyl)-5 - fluoro—l -methyl-1H—pyrazole—4-carboxamide, (1 5. 174) N—[3 -ch10rofluoro-6—(trifluoromethyl)benzyl]-N- cyclopropyl—3—(difluoromethyl)—5-fluoro-l-methy1-1H—pyrazole—4-carboxamide, (15.175) N—cyclopropyl- 3-(difluoromethyl)-N—(2—ethy1-4,5-dimethylbenzyl)flu0ro-1 -methyl—1H-pyrazole—4-carboxamide, (15.176) N—cyclopropy1—3 -(difluoromethyl)fluoro-N-(2-isopropylbenzyl)methyl-lH—pyrazol hioamide, (15.177) 3-(difluoromethyl)-N—(7-fluoro-1 ,1,3 -trimethyl—2,3-dihydro—1H—inden-4—y1)-1 - methyl-1H—pyrazolecarboxamide, (15. 178) 3-(difluoromethyl)-N—[(3R)fluoro-1 ,1,3—trimethyl—2,3 - dihydro- 1 H—indenyl] -1 -methyl-1H-pyrazole-4—carboxamide, (1 5. 1 79) 3-(difluoromethyl)—N- [(3 S) fluoro-l ,1 ,3—trimethyl—2,3-dihydro-1H—inden—4-yl]—l-methy1—1H-pyrazolecarboxamide, (15.1 80) N'- (2,5-dimethylphenoxyphenyl)—N—ethyl-N—methylimidoformamide, (1 5 - . 1 8 l) N'- {4-[(4,5 oro-1 ,3 thiazoly1)oxy] -2,5-dimethy1pheny1} -N-ethyl-N—methylimidoformamide, (15.1 82) N-(4-chloro-2,6- difluorophcnyl)—4-(2—chlorofluorophenyl)-1 ,3-dimethyl-1H—pyrazole-5~amine. All the mixing partners mentioned in classes (1) to (15), as the case may be, may form salts with suitable bases or acids if they are capable of doing so on the basis of their functional groups.
Biological pesticides as mixing components The compounds of the formula (I) can be combined with biological pesticides.
Biological pesticides include especially bacteria, fungi, yeasts, plant extracts and products formed by microorganisms, including proteins and secondary metabolites.
Biological pesticides include ia such as spore-forming ia, root-colonizing bacteria and bacteria which act as biological insecticides, ides or nematicides.
Examples of such bacteria which are used or can be used as biological ides are: Bacillus iquefaciens, strain FZB42 (DSM 231179), or Bacillus cereus, especially B. cereus strain CNCM I-1562 or Bacillusfirmus, strain I—1582 (Accession number CNCM I—1582) or Bacillus pumilus, ally strain GB34 (Accession No. ATCC 700814) and strain QST2808 (Accession No. NRRL B- 30087), or Bacillus subtilis, especially strain GB03 (Accession No. ATCC SD-1397), or Bacillus subtilis VVO 2015/067647 — 89 - strain QST713 (Accession No. NRRL B-21661) or Bacillus subtilis strain OST 30002 (Accession No.
NRRL B—50421) Bacillus t/mringiensis, especially B. thuringiensis subspecies israelensis (serotype H- 14), strain AM65-52 (Accession No. ATCC 1276), or B. giensz‘s subsp. aizawai, especially strain 857 (SD—1372), or B. thuringiensis subsp. kurstaki strain HD-l, or B. giensis subsp. tenebrionis strain NB 176 (SD-5428), ria penetrans, Pasteuria spp. (Rotylenchulus reniformis nematode)~PR3 (Accession Number ATCC SD-5834), Streptomyces microflavus strain AQ6121 (= QRD 31.013, NRRL B-50550), Streptomyces galbus strain AQ 6047 (Accession Number NRRL 30232).
Examples of fungi and yeasts which are used or can be used as biological pesticides are: Beauveria bassiana, especially strain ATCC 74040, Coniothyrium minitans, especially strain CON/M/91-8 (Accession No. DSM—9660), Lecanicillium spp., especially strain HRO LEC 12, Lecanicillium lecam‘i, (formerly known as Verticillium lecanii), especially strain KV01, Metarhizium anisopliae, especially strain F52 84/ ATCC 90448), Metschnikowiafructicola, especially strain NRRL 2, Paecilomycesfumosoroseus (now: Isariafumosorosea), especially strain [FPC 200613, or strain Apopka 97 (Accesion No. ATCC 20874), Paecilomyces nus, especially P. nus strain 251 (AGAL 89/030550), myces flavus, especially strain V117b, derma atroviride, especially strain SCl (Accession Number CBS 122089), Trichoderma harzianum, especially T. harzianum rifaz' T39 (Accession Number CNCM L952).
Examples of viruses which are used or can be used as biological pesticides are: Adoxophyes orana (summer fruit tortrix) granulosis virus (GV), Cydia pomonella (codling moth) granulosis virus (GV), Helicoverpa armigera (cotton bollworm) nuclear polyhedrosis virus (NPV), Spodoptera exigua (beet armyworm) mNPV, tera frugiperda (fall armyworm) mNPV, Spodoptera littoralis (African cotton leafworm) NPV.
Also included are bacteria and fungi which are added as 'inoculant' to plants or plant parts or plant organs and which, by virtue of their particular properties, promote plant growth and plant health.
Examples include: cterium Spp., Azorhizobium caulinodans, rillum spp., Azotobacter spp., hz'zobium known as Pseudomonas cepacia), spp., Bur/(holderia spp., especially Burkholderz'a a (formerly Gigaspora spp., or Gigaspora monosporum, Glomus spp., Laccaria Spp., Lactobacillus buchneri, Paraglomus Spp., Pisolithus tinctorus, Pseudomonas spp., Rhizobium spp., especially Rhizobium z'i, Rhizopogon spp., Scleroderma spp., Suillus Spp., Streptomyces spp.
Safcncrs as mixing components The compounds of the formula (I) can be combined with rs, for example benoxacor, cloquintocet (—mexy1), cyometrinil, cyprosulfamide, dichlormid, fenchlorazole (~ethyl), fenclorim, flurazole, fluxofenim, furilazole, isoxadifen (—ethyl), yr (~diethyl), naphthalic anhydride, oxabetrinil, 2—methoxy-N—({4-[(methylcarbamoy1)amino]phenyl}sulphonyl)benza1nide (CAS 129531- 12-0), 4—(dichloroacetyl)-l—oxaazaspiro[4.5]decane (CAS 715263), 2,2,5—trimethyl (dichloroacetyl)—1,3-oxazolidine (CAS 528364).
Plants and parts of plants All plants and parts of plants can be treated in ance with the ion. Plants are understood here to mean all plants and populations of plants, such as ble and undesirable wild plants or crop plants (including naturally occurring crop plants), for e cereals (wheat, rice, triticale, barley, rye, oats), maize, soya bean, potato, sugar beet, sugar cane, tomatoes, peas and other vegetable species, cotton, tobacco, oilseed rape, and also fruit plants (with the fruits apples, pears, citrus fruits and grapevines). Crop plants may be plants which can be obtained by conventional breeding and optimization methods or by biotechnological and genetic engineering methods or combinations of these methods, ing the transgenic plants and including the plant cultivars which are protectable and non- table by plant breeders’ rights. Parts of plants shall be understood to mean all parts and organs of the plants above and below ground, such as shoot, leaf, flower and root, examples given being leaves, needles, stalks, stems, flowers, fruit bodies, fruits and seeds, and also tubers, roots and rhizomes. Parts of plants also include harvested material and vegetative and generative propagation material, for example cuttings, tubers, rhizomes, slips and seeds.
The inventive treatment of the plants and parts of plants with the compounds of the formula (I) is effected directly or by allowing them to act on the surroundings, habitat or storage space thereof by the customary treatment s, for example by dipping, spraying, evaporating, fogging, scattering, painting on, injecting, and, in the case of propagation material, especially in the case of seeds, also by applying one or more coats.
As already mentioned above, it is possible in accordance with the invention to treat all plants and parts thereof. In a preferred embodiment, wild plant species and plant cultivars, or those ed by conventional biological breeding, such as crossing or last fusion, and parts thereof, are treated. In a further preferred embodiment, transgenic plants and plant cultivars obtained by genetic engineering s, if appropriate in combination with tional methods (genetically modified organisms), and parts thereof are treated. The term " or "parts of plants" or "plant parts" has been explained above. Particular preference is given in ance with the invention to treating plants of the respective commercially customary cultivars or those that are in use. Plant cultivars are understood to mean plants having new properties ts") and which have been obtained by conventional ng, by nesis or by recombinant DNA techniques. They may be cultivars, varieties, biotypes or genotypes.
W0 2015/067647 'I‘ransocnic )lants seed treatment and intcuralion events The preferred transgenic plants or plant cultivars (those obtained by genetic engineering) which are to be d in accordance with the invention include all plants which, through the genetic modification, received genetic material which imparts ular advantageous useful traits to these plants. Examples of such properties are better plant , increased tolerance to high or low temperatures, increased tolerance to t or to levels of water or soil salinity, enhanced flowering performance, easier harvesting, accelerated ripening, higher yields, higher quality and/or higher nutritional value of the harvested products, better storage life and/0r processibility of the harvested products. Further and particularly emphasized examples of such ties are increased resistance of the plants against animal and microbial pests, such as against insects, arachnids, nematodes, mites, slugs and snails owing, for example, to toxins formed in the plants, in particular those formed in the plants by the genetic material from Bacillus thuringiensis (for example by the genes CryIA(a), CryIA(b), CryIA(c), CryIlA, CryIIIA, CryIIIBZ, Cry9c Cry2Ab, Cry3Bb and CryIF and also combinations thereof), and also increased resistance of the plants against phytopathogenic fungi, bacteria and/or viruses caused, for example, by systemic acquired resistance (SAR), systemin, lexins, elicitors and resistance genes and correspondingly expressed proteins and toxins, and also increased tolerance of the plants to certain active herbicidal ingredients, for e imidazolinones, sulphonylureas, glyphosate or phosphinothricin (for example the "PAT" gene). The genes which impart the desired traits in on may also be present in combinations with one another in the transgenic plants. Examples of transgenic plants include the ant crop plants, such as cereals (wheat, rice, triticale, barley, rye, oats), maize, soya beans, potatoes, sugar beet, sugar cane, tomatoes, peas and other types of vegetable, cotton, tobacco, oilseed rape and also fruit plants (with the fruits apples, pears, citrus fruits and grapes), particular emphasis being given to maize, soya beans, wheat, rice, potatoes, cotton, sugar cane, tobacco and d rape. Traits which are ularly emphasized are the increased resistance of the plants to insects, arachnids, des and slugs and .
Crop protection ~ types of treatment The treatment of the plants and plant parts with the compounds of the a (I) is effected directly or by action on their surroundings, habitat or storage space by the customary treatment methods, for example by dipping, spraying, atomizing, irrigating, evaporating, dusting, fogging, broadcasting, foaming, painting, spreading-on, injecting, watering (drenching), drip irrigating and, in the case of propagation material, ally in the case of seed, also by dry seed treatment, wet seed ent, slurry treatment, incrustation, coating with one or more coats, etc. It is also possible to deploy the compounds of the formula (I) by the low volume method or to inject the use form or the compound of the formula (I) itself into the soil. ‘ - 92 — A preferred direct treatment of the plants is foliar application, meaning that the compounds of the formula (I) are applied to the foliage, where ent frequency and application rate should be adjusted according to the level of infestation with the pest in question.
In the case of ically active compounds, the compounds of the a (I) also get into the plants via the root system. The plants are then treated by the action of the compounds of the a (I) on the habitat of the plant. This can be accomplished, for example, by drenching, or by mixing into the soil or the nutrient solution, meaning that the locus of the plant (e.g. soil or hydroponic s) is impregnated with a liquid form of the compounds of the a (I), or by soil application, meaning that the compounds of the formula (I) are introduced in solid form (e.g. in the form of granules) into the locus of the . In the case of paddy rice crops, this can also be accomplished by metering the compound of the formula (I) in a solid application form (for example as granules) into a flooded paddy field.
Seed treatment The control of animal pests by the treatment of the seed of plants has long been known and is the t of constant improvement. However, the treatment of seed entails a series of problems which cannot always be solved in a satisfactory manner. Thus, it is desirable to p s for protecting the seed and the germinating plant which dispense with, or at least reduce considerably, the additional application of pesticides during storage, after sowing or after emergence of the plants. It is additionally desirable to optimize the amount of active ingredient used so as to provide optimum protection for the seed and the germinating plant from attack by animal pests, but without damage to the plant itself by the active ingredient used. In particular, methods for the treatment of seed should also take account of the intrinsic insecticidal or nematicidal properties of pest-resistant or -tolerant transgenic plants in order to achieve optimal tion of the seed and the germinating plant with a minimum expenditure of crop protection products. id="p-253" id="p-253" id="p-253" id="p-253" id="p-253" id="p-253"
[253] The present invention therefore also relates, more particularly, to a method for protection of seed and germinating plants from attack by pests, by ng the seed with one of the compounds of the formula (I). The inventive method for protecting seed and germinating plants against attack by pests further comprises a method in which the seed is treated aneously in one operation or sequentially with a compound of the formula (I) and a mixing component. It also comprises a method where the seed is treated at different times with a compound of the formula (I) and a mixing component.
The invention likewise relates to the use of the compounds of the formula (I) for treatment of seed for protection of the seed and the resulting plant from animal pests. [25 5] The invention further relates to seed which has been treated with a compound of the formula (I) for protection from animal pests. The invention also relates to seed which has been treated simultaneously with a compound of the a (I) and a mixing component. The invention further Vt’O 2015/067647 2014/073795 relates to seed which has been treated at different times with a compound of the formula (I) and a mixing component. In the case of seed which has been treated at different times with a compound of the formula (I) and a mixing component, the individual substances may be present on the seed in different layers. In this case, the layers comprising a compound of the a (I) and mixing components may optionally be separated by an intermediate layer. The invention also relates to seed in which a compound of the formula (I) and a mixing ent have been applied as part of a coating or as a r layer or further layers in addition to a coating.
The invention further relates to seed which, after the treatment with a compound of the formula (I), is subjected to a film-coating process to prevent dust abrasion on the seed. id="p-257" id="p-257" id="p-257" id="p-257" id="p-257" id="p-257"
[257] One of the advantages that occur when one of the compounds of the formula (1) acts systemically is that the treatment of the seed protects not only the seed itself but also the plants resulting therefrom, after emergence, from animal pests. In this way, the immediate treatment of the crop at the time of sowing or shortly thereafter can be dispensed with. [25 8] A further advantage is that the treatment of the seed with a compound of the formula (I) can enhance germination and emergence of the treated seed.
It is likewise considered to be advantageous that compounds of the formula (I) can ally also be used for transgenic seed.
Compounds of the formula (I) can also be used in combination with ling logy compositions, which results, for example, in better colonization by symbionts, for example rhizobia, mycorrhizae and/or endophytic bacteria or fungi, and/or in optimized nitrogen fixation.
The compounds of the formula (I) are suitable for protection of seed of any plant variety which is used in agriculture, in the greenhouse, in forests or in horticulture. More particularly, this es seed of cereals (for example wheat, barley, rye, millet and oats), corn, cotton, soya beans, rice, potatoes, sunflowers, , tobacco, canola, oilseed rape, beets (for example sugarbeets and fodder beets), peanuts, vegetables (for example es, cucumbers, beans, cruciferous vegetables, onions and lettuce), fruit plants, lawns and ntal plants. Of ular significance is the treatment of the seed of cereals (such as wheat, barley, rye and oats), maize, soya, cotton, canola, oilseed rape and rice.
As already mentioned above, the treatment of transgenic seed with a nd of the formula (I) is also of particular significance. This involves the seed of plants which generally contain at least one heterologous gene which controls the expression of a polypeptide having insecticidal and/or nematicidal properties in particular. The logous genes in transgenic seed may originate from microorganisms such as Bacillus, Rhizobium, Pseudomonas, Serratia, Trichoderrna, Clavibacter, Glomus or Gliocladium. The present invention is particularly suitable for the treatment of transgenic seed — 94 - ning at least one heterologous gene originating from Bacillus sp. The heterologous gene is more preferably derived from Bacillus thuringiensis.
In the context of the present invention, the compound of the formula (I) is applied to the seed.
The seed is preferably treated in a state in which it is sufficiently stable for no damage to occur in the course of treatment. In general, the seed can be treated at any time between harvest and sowing. It is customary to use seed which has been separated from the plant and freed from cobs, shells, , coats, hairs or the flesh of the fruits. For example, it is possible to use seed which has been harvested, d and dried down to a moisture content which allows storage. Alternatively, it is also possible to use seed which, after drying, has been treated with, for e, water and then dried again, for example priming. id="p-264" id="p-264" id="p-264" id="p-264" id="p-264" id="p-264"
[264] In l, in the treatment of the seed, it has to be ensured that the amount of the compound of the formula (I) and/or r additives applied to the seed is chosen such that the germination of the seed is not impaired and the plant which arises therefrom is not damaged. This has to be d particularly in the case of active ingredients which can exhibit phytotoxic effects at certain ation rates. id="p-265" id="p-265" id="p-265" id="p-265" id="p-265" id="p-265"
[265] The compounds of the formula (I) are generally applied to the seed in a le formulation.
Suitable formulations and processes for seed treatment are known to the person skilled in the art.
The compounds of the formula (I) can be converted to the customary seed dressing formulations, such as solutions, ons, suspensions, powders, foams, es or other coating compositions for seed, and also ULV formulations. id="p-267" id="p-267" id="p-267" id="p-267" id="p-267" id="p-267"
[267] These ations are produced in a known manner, by mixing the compounds of the formula (I) with customary additives, for example customary extenders and solvents or ts, dyes, wetters, dispersants, emulsifiers, antifoams, preservatives, ary thickeners, stickers, gibberellins and also water.
Useful dyes which may be present in the seed dressing formulations usable in accordance with the invention are all dyes which are customary for such purposes. It is possible to use either pigments, which are sparingly soluble in water, or dyes, which are soluble in water. Examples include the dyes known by the names Rhodamine B, CI. Pigment Red 112 and Cl. Solvent Red 1.
Useful wetters which may be present in the seed dressing formulations usable in accordance with the invention are all substances which promote wetting and which are conventionally used for the formulation of active agrochemical ingredients. Preference is given to using alkyl naphthalenesulphonates, such as diisopropyl or diisobutyl naphthalenesulphonates.
Useful dispersants and/or fiers which may be present in the seed dressing formulations usable in accordance with the invention are all nonionic, anionic and cationic dispersants conventionally ‘ - 95 — used for the formulation of active agrochemical ingredients. Preference is given to using nonionic or anionic dispersants or es of nonionic or anionic dispersants. Suitable nonionic dispersants include in particular ethylene oxide/propylene oxide block polymers, alkylphenol polyglycol ethers and tristryrylphenol polyglycol ethers, and the phosphated or sulphated derivatives thereof. Suitable anionic dispersants are especially ulphonates, polyacrylic acid salts and arylsulphonate/forrnaldehyde condensates.
Antifoams which may be t in the seed dressing ations usable in ance with the invention are all foam-inhibiting substances tionally used for formulation of active agrochemical ingredients. Silicone antifoams and magnesium stearate can be used with preference. id="p-272" id="p-272" id="p-272" id="p-272" id="p-272" id="p-272"
[272] Preservatives which may be t in the seed dressing formulations usable in accordance with the invention are all substances usable for such purposes in agrochemical compositions. Examples include dichlorophene and benzyl alcohol hemiformal.
Secondary thickeners which may be present in the seed dressing formulations usable in accordance with the invention are all substances which can be used for such purposes in agrochemical compositions. Preferred examples include cellulose derivatives, acrylic acid derivatives, xanthan, modified clays and finely divided silica.
Useful stickers which may be present in the seed dressing formulations usable in accordance with the invention are all customary binders usable in seed dressing products. Preferred examples include polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol and tylose. id="p-275" id="p-275" id="p-275" id="p-275" id="p-275" id="p-275"
[275] Gibberellins which may be present in the seed dressing formulations usable in ance with the ion are preferably the gibberellins Al, A3 (= gibberellic acid), A4 and A7; particular preference is given to using gibberellic acid. The gibberellins are known (cf. R. Wegler e der Pflanzenschutz- und Schadlingsbekampfungsmittel" stry of the Crop Protection Compositions and Pesticides], vol. 2, Springer Verlag, 1970, p. 401-412). id="p-276" id="p-276" id="p-276" id="p-276" id="p-276" id="p-276"
[276] The seed dressing ations usable in accordance with the invention can be used to treat a wide variety of different kinds of seed, either directly or after prior dilution with water. For instance, the concentrates or the preparations obtainable therefrom by dilution with water can be used to dress the seed of cereals, such as wheat, barley, rye, oats, and triticale, and also the seed of maize, rice, oilseed else a wide variety of different vegetable rape, peas, beans, cotton, sunflowers, soya beans and beets, or seed. The seed ng formulations usable in accordance with the invention, or the dilute use forms thereof, can also be used to dress seed of transgenic plants.
For treatment of seed with the seed ng formulations usable in accordance with the invention, or the use forms prepared therefrom, all mixing units usable arily for the seed dressing are useful. Specifically, the procedure in seed dressing is to place the seed into a mixer in batchwise or V40 2015/067647 — 96 - continuous operation, to add the particular desired amount of seed dressing formulations, either as such or after prior dilution with water, and to mix until the formulation is distributed homogeneously on seed. If appropriate, this is followed by a drying operation.
The application rate of the seed dressing formulations usable in accordance with the invention can be varied within a relatively wide range. It is guided by the particular content of the compounds of the formula (I) in the formulations and by the seed. The application rates of the compound of the formula (I) are generally between 0.001 and 50 g per kilogram of seed, preferably between 0.01 and 15 g per kilogram of seed.
Use in animal health id="p-279" id="p-279" id="p-279" id="p-279" id="p-279" id="p-279"
[279] In the animal health sector, i.e. in the field of veterinary medicine, the active ingredients according to the present ion act against animal parasites, especially ectoparasites or else, in a further embodiment, endoparasites. The term "endoparasites" includes especially helminths such as cestodes, nematodes or odes, and protozoa such as coccidia. Ectoparasites are typically and ably pods, ally insects such as flies (biting and licking), parasitic fly larvae, lice, hair lice, bird lice, fleas and the like; or acarids such as ticks, for example hard ticks or soft ticks, or mites such as scab mites, harvest mites, bird mites and the like, and also aquatic ectoparasites such as copepods.
In the field of veterinary medicine, the compounds of the formula (I) having favourable homeotherm toxicity are suitable for controlling parasites which occur in animal breeding and animal husbandry in livestock, breeding s, zoo animals, laboratory animals, experimental animals and domestic animals. They are active against all or specific stages of development of the parasites.
Agricultural livestock e, for example, mammals such as sheep, goats, horses, donkeys, camels, buffalo, rabbits, er, fallow deer, and particularly cattle and pigs; poultry such as s, ducks, for example in aquaculture, and also geese, and particularly ns; fish and crustaceans, insects such as bees.
Domestic animals include, for example, mammals, such as hamsters, guinea pigs, rats, mice, chinchillas, ferrets, and particularly dogs, cats, cage birds, reptiles, ians and aquarium fish.
In a preferred embodiment, the compounds of the formula (I) are administered to mammals.
In another preferred embodiment, the nds of the formula (I) are administered to birds, namely caged birds and particularly poultry.
Use of the nds of the formula (I) for the control of animal parasites is intended to reduce or t illness, cases of deaths and reductions in performance (in the case of meat, milk, wool, hides, ‘ animal keeping is enabled and better eggs, honey and the like), such that more economical and simpler animal well-being is achievable.
In relation to the animal health field, the term "control" or "controlling" means that the compounds of the formula (I) are effective in reducing the incidence of the particular parasite in an animal infected with such parasites to an innocuous degree. More specifically, olling" in the present context means that the nd of the formula (I) can kill the respective parasite, inhibit its growth, or inhibit its proliferation.
These tes include: From the order of the Anoplurida, for example, Haematopinus spp., athus spp., Pediculus spp., Phthirus spp., Solenopotes spp.; specific examples are: Linognathus setosus, Linognathus vituli, Linognathus ovillus, Linognathus oviformis, Linognathus pedalis, Linognathus stenopsis, Haematopinus asini macrocephalus, Haematopinus eurysternus, Haematopinus suis, Pediculus humanus capitis, Pediculus humanus corporis, Phylloera vastatrix, Phthirus pubis, Solenopotes capillatus; From the order of the hagida and the suborders Amblycerina and Ischnocerina, for example, Trimenopon spp., Menopon spp., Trinoton spp., Bovicola spp., Werneckiella spp., ntron spp., Damalina spp., Trichodectes spp., la spp., specific examples are: Bovicola bovis, Bovicola ovis, Bovicola limbata, Damalina bovis, Trichodectes canis, Felicola subrostratus, Bovicola caprae, Lepikentron ovis, Werneckiella equi; From the order of the Diptera and the suborders Nematocerina and Brachycerina, for example, Aedes Phlebotomus spp., Lutzomyia spp., spp., Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Culicoides spp., Chrysops spp., Odagmia spp., Wilhelmia spp., Hybomitra spp., Atylotus spp., Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., hrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp., Gasterophilus spp., osca spp., Lipoptena spp., Melophagus spp., Rhinoestrus spp., Tipula spp.; specific examples are: Aedes aegypti, Aedes albopictus, Aedes taeniorhynchus, Anopheles gambiae, Anopheles maculipennis, Calliphora erythrocephala, Chrysozona pluvialis, Culex quinquefasciatus, Culex pipiens, Culex is, Fannia canicularis, Sarcophaga camaria, Stomoxys calcitrans, Tipula paludosa, Lucilia cuprina, Lucilia sericata, Simulium reptans, Phlebotomus papatasi, Phlebotomus longipalpis, Odagmia ornata, Wilhelmia equina, Boophthora erythrocephala, Tabanus bromius, s terus, Tabanus atratus, Tabanus sudeticus, tra ciurea, Chrysops caecutiens, Chrysops relictus, opota pluvialis, Haematopota italica, Musca autumnalis, Musca ica, Haematobia irritans irritans, Haematobia irritans exigua, obia stimulans, Hydrotaea irritans, Hydrotaea albipuncta, mya chloropyga, Chrysomya bezziana, Oestrus ovis, Hypoderma bovis, Hypoderma um, Przhevalskiana silenus, Dermatobia hominis, agus ovinus, Lipoptena capreoli, ena cervi, Hippobosca VVO 2015/067647 - 98 — variegata, Hippobosca equina, Gasterophilus inalis, Gasterophilus haemorroidalis, Gasterophilus inermis, Gasterophilus nasalis, Gasterophilus nigricornis, Gasterophilus pecorum, Braula coeca; From the order of the Siphonapterida, for example, Pulex spp., Ctenocephalides spp., Tunga spp., Xenopsylla spp., Ceratophyllus spp.; specific examples are: Ctenocephalides canis, ephalides felis, Pulex irritans, Tunga penetrans, Xenopsylla cheopis; From the order of the Heteropterida, for example, Cimex spp., ma spp., Rhodnius spp., Panstrongylus spp.
From the order of the Blattarida, for example, Blatta orientalis, Periplaneta americana, Blattela germanica and Supella spp. (e. g. la longipalpa); From the ss of the Acari (Acarina) and the orders of the Meta- and Mesostigmata, for example, Argas spp., odorus spp., Otobius spp., Ixodes spp., mma spp., ephalus (Boophilus) spp., Dermacentor spp., Haemophysalis spp., Hyalomma spp., Dermanyssus spp., Rhipicephalus spp. (the original genus of multihost ticks), Ornithonyssus spp., Pneumonyssus spp., Raillietia spp., Pneumonyssus spp., Sternostoma spp., Varroa spp., Acarapis spp.; specific examples are: Argas persicus, Argas reflexus, Ornithodorus moubata, Otobius megnini, Rhipicephalus (Boophilus) microplus, Rhipicephalus (Boophilus) decoloratus, Rhipicephalus (Boophilus) annulatus, Rhipicephalus (Boophilus) calceratus, Hyalomma anatolicum, Hyalomma aegypticum, Hyalomma marginatum, Hyalomma transiens, Rhipicephalus evertsi, Ixodes ricinus, Ixodes hexagonus, Ixodes canisuga, Ixodes pilosus, Ixodes ndus, Ixodes scapularis, Ixodes holocyclus, Haemaphysalis concinna, Haemaphysalis punctata, hysalis cinnabarina, Haemaphysalis otophila, Haemaphysalis leachi, Haemaphysalis orni, Dermacentor marginatus, Dermacentor reticulatus, Dermacentor pictus, Dermacentor albipictus, Dermacentor andersoni, Dermacentor variabilis, Hyalomma mauritanicum, Rhipicephalus sanguineus, Rhipicephalus bursa, Rhipicephalus appendiculatus, Rhipicephalus capensis, Rhipicephalus turanicus, Rhipicephalus zambeziensis, Amblyomma americanum, Amblyomma variegatum, Amblyomma tum, Amblyomma hebraeum, Amblyomma cajennense, yssus gallinae, Ornithonyssus bursa, Ornithonyssus sylviarum, Varroa jacobsoni; From the order of the Actinedida (Prostigmata) and Acaridida (Astigmata), for example, Acarapis spp., Cheyletiella spp., ocheyletia spp., Myobia spp., Psorergates spp., Demodex spp., Trombicula spp., Listrophorus spp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypodectes spp., Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., ocoptes spp., Cytodites spp. and Laminosioptes spp.; specific examples are: Cheyletiella i, Cheyletiella blakei, Demodex canis, Demodex bovis, Demodex ovis, Demodex , x equi, Demodex caballi, x suis, Neotrombicula autumnalis, Neotrombicula desaleri, Neoschongastia xerothermobia, Trombicula akamushi, Otodectes s, Notoedres cati, Sarcoptis canis, tes bovis, Sarcoptes ovis, Sarcoptes rupicaprae (=S. caprae), Sarcoptes equi, Sarcoptes suis, Psoroptes ovis, Psoroptes ‘ — 99 — 2014/073795 cuniculi, Psoroptes equi, Chorioptes bovis, Psoergates ovis, Pneumonyssoidic mange, Pneumonyssoides m, Acarapis woodi.
From the subclass of the copepods with the order of the Siphonostomatoida in particular the genera htheirus and Caligus; the species Lepeophtheirus salmonis, Caligus elongatus and Caligus clemensi may be mentioned by way of example and with particular preference.
In general, the inventive active ingredients can be employed directly when they are used for the treatment of animals. They are preferably ed (administered) in the form of pharmaceutical compositions which may comprise pharmaceutically acceptable excipients and/or auxiliaries known in the prior art. id="p-289" id="p-289" id="p-289" id="p-289" id="p-289" id="p-289"
[289] In the sector of animal health and in animal husbandry, the active ingredients are employed (=administered) in a known manner, by enteral stration in the form of, for example, tablets, capsules, potions, drenches, granules, pastes, boluses, the feed—through process and suppositories, by parenteral administration, for example by injection (intramuscular, subcutaneous, intravenous, eritoneal inter alia), implants, by nasal administration, by dermal administration in the form, for example, of dipping or bathing, spraying, pouring on and spotting on, washing and powdering, and also with the aid of moulded articles containing the active ingredient, such as collars, earmarks, tailmarks, limb bands, halters, marking devices, etc. The active ingredients can be formulated as a shampoo or as suitable formulations applicable in aerosols or unpressurized sprays, for example pump sprays and atomizer sprays, id="p-290" id="p-290" id="p-290" id="p-290" id="p-290" id="p-290"
[290] In the case of employment for livestock, poultry, domestic pets, etc., the inventive active ingredients can be employed as ations (for example powders, wettable powders ["WP"], emulsions, emulsifiable concentrates ["EC"], free-flowing compositions, homogeneous solutions and suspension trates ["SC"]), which contain the active ients in an amount of 1% to 80% by weight, directly or after dilution (e.g. 100- to 10 1d on), or they can be used as a chemical bath.
In the case of use in the animal health sector, the inventive active ients, in order to n the spectrum of activity, can be used in combination with suitable ists, repellents or other active ingredients, for example acaricides, insecticides, anthelmintics, rotozoal agents. Potential mixing components for inventive compounds of the formula (I) may, in the case of applications in animal health, be one or more nds from groups (In-1) to (In-25).
(In-1) Acetylcholinesterase (AChE) inhibitors, for e carbamates, e.g. alanycarb, rb, bendiocarb, benfilracarb, butocarboxim, butoxycarboxirn, carbaryl, carbofuran, carbosulfan, encarb, fenobucarb, formetanate, furathiocarb, isoprocarb, methiocarb, methomyl, metolcarb, oxamyl, pirirnicarb, propoxur, thiodicarb, nox, triazamate, trimethacarb, XMC and xylylcarb; particular preference is given here, for applications against ectoparasites, to bendiocarb, carbaryl, methomyl, promacyl and propoxur; or VVO 2015/067647 — 100 — organophosphates, e.g. acephate, azamethiphos, os (-methyl, -ethy1), cadusafos, chlorethoxyfos, chlorfenvinphos, chlormephos, chlorpyrifos yl), coumaphos, cyanophos, demeton-S—methyl, on, dichlorvos/DDVP, dicrotophos, dimethoate, dimethylvinphos, disulfoton, EPN, ethion, ophos, famphur, phos, fenitrothion, fenthion, fosthiazate, heptenophos, isofenphos, isopropyl O-(methoxyaminothiophosphoryl) salicylate, isoxathion, malathion, mecarbam, idophos, methidathion, mevinphos, monocrotophos, naled, omethoate, oxydemeton—methyl, parathion, parathion-methyl, phenthoate, phorate, phosalone, t, phosphamidon, phoxim, pirimiphos (-methyl), profenofos, propetamphos, prothiofos, pyraclofos, pyridaphenthion, quinalphos, sulfotep, tebupirimfos, temephos, os, tetrachlorvinphos, ton, triazophos, triclorfon and vamidothion; particular preference is given here, for applications against ectoparasites, to azamethiphos, chlorfenvinphos, chlorpyrifos, coumaphos, cythioate, diazinon (dimpylate), dichlorvos (DDVP), dicrotophos, dimethoate, ethion (diethion), famphur (famophos), fenitrothion, on (MPP), heptenophos, malathion, naled, phosmet (PMP, phtalofos) phoxim, propetamphos, os, tetrachlorvinphos (CVMP) and triclorfon/metrifonate.
(In-2) GABA-gated de channel antagonists, for example organochlorines, e.g. bromocyclene, chlordane and endosulfan (alpha-), heptachlor, lindane and toxaphene; particular preference is given here, for applications against ectoparasites, to endosulfan (alpha-) and lindane; or frproles (phenylpyrazoles), e.g. acetoprole, ethiprole, fipronil, pyrafluprole, pyriprole, rizazole; particular preference is given here, for applications against ectoparasites, to fipronil and pyriprole; or arylisoxazolines, arylpyrrolines, rrolidines, e.g. fluralaner (known from WO2009/2024541, ex. 11-1; but also nds from W02012007426, W02012042006, W02012042007, W02012107533, W02012120135, W02012165186, W02012155676, WO2012017359, WO2012127347, W02012038851, WO2012120399, WO2012156400, W02012163959, W02011161130, WO2011073444, W02011092287, W02011075591, W02011157748, WO 2007/075459, W0 25984, W0 2005/085216, WO 2009/002809), afoxolaner (e. g. in WO2011149749) and structurally related arylpyrrolines (known, for e, from W02009/072621, WO 2010020522, WO 2009112275, WO 2009097992, WO 2009072621, JP 2008133273, JP 2007091708), or arylpyrrolidines (e.g. in W02012004326, WO2012035011, WO2012045700, WO 2010090344, WO 2010043315, WO 2008128711, JP 0971), and compounds from the group of the so-called metadiamides (known, for example, from W02012020483, 020484, W02012077221, W020 1 20693 66, WO2012175474, W02011095462, W02011113756, W02011093415, 073165); particular preference is given here, for applications against ectoparasites, to afoxolaner and fluaralaner.
(In-3) Sodium channel modulators/voltage-gated sodium l blockers, for example pyrethroids, e. g. acrinathrin, allethrin (d-cis-trans, d—trans), bifenthrin, ethrin, bioallethrin opentenyl, bioresmethrin, cycloprothrin, cyfluthrin (beta—), cyhalothrin (gamma-, lambda-), cypermethrin (alpha-, \‘x’O‘ 67647 -101 » PCT/EPZGH/(WS'FQS beta-, theta-, zeta—), cyphenothrin [(1R)-trans isomer], deltamethrin, dimefluthrin, empenthrin [(EZ)- (1R) isomer], esfenvalerate, prox, fenpropathrin, fenvalerate, flucythrinate, flumethrin, fluvalinate (tau—), halfenprox, imiprothrin, metofluthrin, perrnethrin, phenothrin [(1R)—trans isomer], prallethrin, hrin, pyrethrins (pyrethrum), resmethrin, RU 15525, silafluofen, tefluthrin, tetramethrin [(lR) isomer)], tralomethrin, transfluthrin and ZXI 8901; particular preference is given here, for applications against ectoparasites, to the type I pyrethroids rin, bioallethrin, permethrin, phenothrin, resmethrin, tetramethrin and the type II pyrethroids (alphacyanopyrethroids) alpha-cypermethrin, rin (beta—), cyhalothrin (lambda-), cypermethrin (alpha-, zeta-), deltamethrin, fenvalerate, rinate, flumethrin, fluvalinate , and the ester-free pyrethroids etofenprox and silafluofen; or organochlorine compounds, e.g. DDT or methoxychlor. Active ingredients from this class are very particularly suitable as mixing components, since they have a longer—lasting contact-repelling action and therefore extend the activity spectrum to include this component.
(In-4) Nicotinergic acetylcholine or agonists, for example otinoids, e.g. acetamiprid, clothianidin, dinotefuran, imidacloprid, imidaclothin, nitenpyram, thiacloprid, thiamethoxam; particular preference is given here, for applications against ectoparasites, to clothianidin, dinotefuran, imidacloprid, yram and thiacloprid; or nicotine.
(In-5) Allosteric acetylcholine or modulators (agonists), for example spinosyns, e.g. spinetoram and ad; particular ence is given here, for applications against ectoparasites, to spinosad and spinetoram .
(In-6) Chloride channel activators, for example avermectins/milbemycins, e.g. abamectin, doramectin, emamectin benzoate, eprinomectin, ivermectin, ctin, lepimectin, milbemycin oxime, milbemectin, moxidectin and selamectin; indole terpenoids, for example sporic acid tives, especially nodulisporic acid A; particular preference is given here, for applications against ectoparasites, to doramectin, eprinomectin, ivermectin, milbemycin oxirne, moxidectin, selamectin and nodulisporic acid A.
(In-7) Juvenile hormone analogues, for e hydroprene (3—), kinoprene, methoprene (8—); or fenoxycarb; pyriproxyfen; particular preference is given here, for applications against ectoparasites, to methoprene (8-) and pyriproxyfen.
(In—8) Mite growth inhibitors, e.g. clofentezine, diflovidazin, hexythiazox, etoxazole; particular ence is given here, for applications against ectoparasites, to etoxazole.
(In—9) 810-1 and latrophilin receptor agonists, for example cyclic depsipeptides, e.g. emodepside and its precursor A (known from EP 382173, nd I); particular preference is given here, for applications against ectoparasites, to emodepside.
) Oxidative phosphorylation inhibitors, ATP disruptors, for example diafenthiuron.
YQHJ ZOLJ/(lL/U-t,r'f‘ '1: "If-him", if}-‘1’, l, ‘\,l/lLL .CilL‘l/Ki/J/L/rb)F‘r‘"/_‘T)‘\ 1'/f'=3'\"'l‘ » ~ (In—12) Nicotinergic choline receptor antagonists, for example bensultap, cartap (hydrochloride), thiocylam, and thiosultap (sodium).
(In-13) Chitin biosynthesis inhibitors, type 0, for example benzoylureas, e. g. bistrifluron, chlorfluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron and triflumuron; particular preference is given here, for applications t ectoparasites, to diflubenzuron, on, lufenuron and triflumuron.
) Chitin biosynthesis inhibitors, type 1, for example buprofezin.
(In-15) Moulting inhibitors, for e zine and dicyclanil; particular preference is given here, for applications against ectoparasites, to cyromazine and dicyclanil.
(In—16) Ecdysone agonists/disruptors, for example diacylhydrazines, e. g. chromafenozide, halofenozide, methoxyfenozide and tebufenozide.
(In-17) Octopaminergic agonists, for example amitraz, cymiazole, chlordimeform and demiditraz; particular preference is given here, for applications against ectoparasites, to z, cymiazole and demiditraz.
(In-18) Complex-III electron transport tors, for e hydrainethylnone; acequinocyl; fluacrypyrim.
(In-19) Complex-I electron transport inhibitors, for example from the group of the METI ides, e.g. fenazaquin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad, tolfenpyrad; particular preference is given here, for applications t ectoparasites, t0 fenpyroximate, pyrimidifen and tolfenpyrad; (In-20) Voltage-gated sodium channel blockers, for example indoxacarb and metaflumizone; particular preference is given here, for applications against ectoparasites, to indoxacarb and metaflumizone.
(In-21) Inhibitors of —CoA carboxylase, for example tetronic acid derivatives, e.g. spirodiclofen and spiromesifen; or tetramic acid derivatives, e.g. spirotetramat.
(In-22) x—II electron transport inhibitors, for example cyenopyrafen.
(In-23) Ryanodine receptor effectors, for example diamides, e.g. flubendiamide, chlorantraniliprole (Rynaxypyr), cyantraniliprole (Cyazypyr) and also 3-bromo—N— {2-bromochloro—6-[(1- cyclopropylethyl)carbamoyl]phenyl} —1 -(3 -chloropyridinyl)— 1 zole—S -carboxamide (known from W02005/077934) or methyl 2-[3,5-dibromo({[3-bromo—l~(3-chloropyridin—2-yl)-1H—pyrazol-S- yl]carbonyl}amino)benzoyl]—1,2-dimethylhydrazinecarboxylate (known from W02007/O43 677).
(In—24) Fuither active ingredients with unknown mechanism of action, for example azadirachtin, amidoflumet, imate, bifenazate, ohinomethionat, te, cyflumetofen, dicofol, fluensulfone (5— "’0' EMS/067647 - 103 — 2014/073795 chloro[(3 ,4,4-trifluorobut-3 —enyl)sulphonyl]—l ,3 -thiazole), flufenerim, pyridalyl and pyrifluquinazon; and additionally ations based on Bacillus finnus 2, BioNeem, Votivo) and the following known active compounds: -bromopyrid—3-yl)methyl](2-fluoroethyl)amino}furan- 2(5H)-one (known from W0 2007/ 1 15644), 4- { [(6-fluoropyrid—3 -yl)methyl](2,2- difluoroethyl)amino}furan—2(5H)-one (known from WO 2007/115644), 4-{[(2-chloro-1,3-thiazol yl)methyl](2-fluoroethyl)amino}furan—2(5H)-one (known from ), 4-{[(6-chloropyrid- ethy1](2—fluoroethyl)amino}furan-2(5H)-one (known from W0 2007/1 15644), 4-{[(6- chloropyridyl)methyl](2,2—difluoroethyl)amino}furan—2(5H)-one (known from ), 4- {[(6-chlorofluoropyIid—3-yl)methyl](methy1)amino}furan-2(5H)-one (known from WC 2007/115643), 4—{[(5,6-dichloropyrid—3—yl)methyl](2-fluoroethyl)amino}furan—2(5H)-one (known from WO 2007/115646), 4-{[(6-chloro-5 -fluoropyridyl)methyl](cyclopropyl)amino}furan—2(5H)—one (known from WC 2007/115643), 4—{[(6—chloropyridyl)methyl](cyclopropyl)amino}filran-2(5H)—one (known from EP-A-0 539 588), -chloropyrid-3 -yl)methyl](methyl)amino}furan-2(5H)-one (known from EP—A—0 539 588), [(6-chloropyridin-3 -yl)methyl](methyl)oxido-?t4- sulphanylidenecyanamide (known from W0 2007/1491 34), [1 —(6-chloropyridin—3- yl)ethyl](methyl)oxido-X4-sulphanylidenecyanamide (known from W0 2007/149134), [(6- trifluoromethylpyridin-3 —yl)methyl](methyl)oxido-lf—sulphanylidenecyanamide (known from WO 2007/095229), sulfoxaflor (likewise known from W0 2007/149134), 11-(4—chloro-2,6-dimethylphenyl)- 12-hydroxy-1,4-dioxaazadispiro[4.2.4.2]tetradec—1l—en-lO-one (known from W0 89633), 3- (4'-fluoro—2,4-dimethylbiphenyl-3 -yl)hydroxy-8—oxa—1-azaspiro[4.5]dec-3 -en-2—one (known from W0 2008/06791 1), 1-[2-fluoro-4—methyl[(2,2,2-trifluoroethyl)sulphinyl]phenyl]-3 -(trifluoromethyl)- 1H—1,2,4—triazolamine (known from WO 2006/043635), [(3S,4aR,12R,12aS,12bS) [(cyclopropylcarbony1)oxy]—6,12-dihydroxy—4, 12b-dimethyl-l 1 -oxo-9—(pyridin-3 -y1)- 1,3 ,4,4a,5,6,6a, l2,12a,12b-decahydro-2H,1 1H—benzo[flpyrano[4,3—b]chromenyl]methyl cyclopropanecarboxylate (known from WO 2006/129714), 2-cyano—3 —(difluoromethoxy)-N-ethyl- benzenesulphonamide (known from WO 2005/035486), N—[l—(2,3-dimethylphenyl)(3,5- ylphenyl)ethyl]-4,5-dihydrothiazolamine (known from W0 2008/104503); penigequinolone A (known from EP 2248422 (compound I) and (compound No. 11).
(In-25) Suitable synergists in the case of use together with ectoparasiticides here include MGK264 (N- octylbicycloheptenecarboxamide), nyl butoxide (PEG) and in; particular preference is given here to piperonyl butoxide and MGK264.
In addition to these , it is also possible to use short—term repellents in mixtures or a combined application. Examples are DEET (N,N-diethylmethylbenzamide), icaridin (1- piperidinecarboxylic acid), (18, 20S)methylpiperidinylcyclohexene-1—carboxamide (S3220), indalone (butyl 3,4-dihydro-2, 2-dimethyloxo-2H—pyran—6-carboxylate), dihydronepetalactones, nootkatone, IR3535 (3-[N—butyl—N—acetyl]-aminopropionic acid ethyl ester), 2-ethylhexane-1,3-diol, (1R,2R,5R)—2—(2—hydroxypropan—2—yl)-5—methyl-cyclohexan—l—ol, dimethyl benzene—l,2-dicarboxylate, ‘ — 104 — dodecanoic acid, undecanone, N,N-diethylphenylacetamide and essential oils or other plant ingredients with known repellent action, for example borneol, callicarpenal, l,8-cineol (eucalyptol), carvacrol, b-citronellol, a-copaene, coumarin (or its synthetic derivatives known from US20120329832).
Icaridin, indalone and IR3535 (3-[N—butyl—N—acetyl]-aminopropionic acid ethyl ester) are particularly preferred for use against ectoparasites.
From the aforementioned groups (1—1) to (1—25), preference is given to the following groups as mixing ents: (In-2), (In-3), (In-4), (In—5), (In-6), (In-17), (In—25).
Particularly preferred examples of insecticidally or acaricidally active compounds, ists or repellents as mixing ents for the inventive compounds of the formula (I) are afoxolaner, allethrin, amitraz, bioallethn'n, chlothianidin, cyfluthrin (beta—), thrin (lambda-), cymiazole, cypermethrin (alpha—, zeta-), cyphenothrin, deltamethrin, demiditraz, furan, doramectin, eprinomectin, etofenprox, fenvalerate, l, fluazuron, flucythrinate, flumethrin, ner, fluvalinate (tau—), icaridin, imidacloprid, iverrnectin, MGK264, milbemycin oxime, ctin, nitenpyram, permethrin, phenothrin, piperonyl butoxide, pyriprole, resmethrin, selamectin, silafluofen, spinetoram, spinosad, tetramethrin, thiacloprid.
Vector control The nds of the formula (I) can also be used in vector control. In the context of the present invention, a vector is an arthropod, especially an insect or arachnid, capable of transmitting pathogens, for example, viruses, worms, -cell organisms and ia, from a reservoir (plant, animal, human, etc.) to a host. The pathogens can be transmitted either mechanically (for example trachoma by non—stinging flies) to a host or after injection (for example malaria parasites by toes) into a host.
Examples of vectors and the diseases or pathogens they transmit are: l) Mosquitoes - Anopheles: malaria, filariasis; - Culex: Japanese encephalitis, sis, other viral diseases, transmission of worms; - Aedes: yellow fever, dengue fever, filariasis, other viral diseases; - idae: transmission of worms, in particular Onchocerca volvulus; 2) Lice: skin infections, ic typhus; 3) Fleas: plague, endemic typhus; \VO 7647 — 105 - PCT/EPZOI4/073795 4) Flies: sleeping sickness (trypanosomiasis); cholera, other bacterial diseases; ) Mites: acariosis, epidemic typhus, rickettsialpox, tularaemia, Saint Louis encephalitis, tick-borne encephalitis (TBE), n—Congo haemorrhagic fever, borreliosis; 6) Ticks: borellioses such as Borrelia duttoni, tick-borne encephalitis, Q fever (Coxiella bumetii), babesioses (Babesia canis canis).
Examples of vectors in the context of the present invention are insects, for example aphids, flies, leaflioppers or thrips, which can transmit plant viruses to plants. Other vectors e of transmitting plant viruses are spider mites, lice, s and nematodes. r examples of vectors in the context of the present invention are insects and arachnids such as mosquitoes, especially of the genera Aedes, Anopheles, for example A. e, A. arabiensis, A. funestus, A. dirus (malaria) and Culex, lice, fleas, flies, mites and ticks, which can transmit pathogens to animals and/or humans.
Vector control is also possible if the compounds of the formula (I) are resistance—breaking.
Compounds of the formula (I) are suitable for use in the prevention of diseases and/or pathogens transmitted by s. Thus, a further aspect of the present invention is the use of compounds of the a (I) for vector control, for example in agriculture, in horticulture, in forestry, in gardens and in leisure facilities, and also in the tion of materials and stored products.
Protection of industrial materials The compounds of the formula (I) are suitable for protecting industrial materials against attack or destruction by insects, for example from the orders Coleoptera, Hymenoptera, Isoptera, Lepidoptera, Psocoptera and oma.
Industrial materials in the present context are tood to mean inanimate materials, such as preferably plastics, adhesives, sizes, papers and cards, leather, wood, processed wood products and coating compositions. The use of the invention for protection of wood is particularly preferred. id="p-303" id="p-303" id="p-303" id="p-303" id="p-303" id="p-303"
[303] In a further embodiment, the compounds of the formula (I) are used together with at least one further insecticide and/or at least one fungicide.
In a r embodiment, the compounds of the formula (I) are in the form of a ready—to-use pesticide, meaning that they can be applied to the al in question without further ations. le further insecticides or ides are in particular those mentioned above. id="p-305" id="p-305" id="p-305" id="p-305" id="p-305" id="p-305"
[305] It has also been found that, surprisingly, the compounds of the formula (I) can be used to protect objects which come into contact with saltwater or brackish water, especially hulls, screens, nets, - 106 — buildings, moorings and signalling systems, against fouling. It is equally le to use the compounds of the formula (I), alone or in combinations with other active ingredients, as antifouling agents.
Control of animal pests in the hygiene sector The compounds of the formula (I) are suitable for controlling animal pests in the hygiene .
More particularly, the invention can be used in the domestic sector, in the hygiene sector and in the protection of stored products, ularly for control of insects, arachnids and mites encountered in enclosed spaces, for e ngs, factory halls, offices, vehicle cabins. For controlling animal pests, the compounds of the formula (I) are used alone or in ation with other active ingredients and/or aries. They are preferably used in domestic insecticide products. The compounds of the formula (I) are effective t sensitive and resistant species, and against all developmental stages.
These pests include, for example, pests from the class Arachnida, from the orders Scorpiones, Araneae and Opiliones, from the classes Chilopoda and Diplopoda, from the class Insecta the order Blattodea, from the orders Coleoptera, tera, Diptera, Heteroptera, Hymenoptera, ra, Lepidoptera, Phthiraptera, Psocoptera, Saltatoria or Orthoptera, aptera and Zygentoma and from the class Malacostraca the order a.
Application is effected, for example, in aerosols, unpressurized spray products, for example pump and atomizer sprays, automatic fogging systems, foggers, foams, gels, evaporator products with evaporator tablets made of cellulose or plastic, liquid evaporators, gel and membrane evaporators, propeller—driven evaporators, energy-free, or e, evaporation systems, moth papers, moth bags and moth gels, as granules or dusts, in baits for spreading or in bait stations.
Preparation processes The inventive compounds can be prepared by customary methods known to those d in the art.
The compounds of the structure (LTD and (I—T2) can be prepared by the methods already described in the literature for analogous compounds: Process I-’l‘l The compounds of the structure (I-Tl) can be prepared by the process specified in Reaction Scheme 1. — 107 - Reaction Scheme 1: .Alkyl O .Alkyl .Alkyl _ O R11b NO Alkyl O Af/A o / Af/Aafi/ko I Al\ 4 A-1 R11a A'2 R N/ 11bl B \ Hydrazine B 83/ E31 / 2~ l B / B )\u 7 J: Rm, BBB, M ",N $1.. R11a R113 A"/ H0A4 A/ A4 A3 \ o Pd(0) A2=A3 A4 A2=A3)\/( ‘A|kyl O‘Alkyl NaOH B B¢ 2‘B 83% 2 ~ '81 R1") 11b 1. Activation B? B|\ A "\B\ /|L1 4\85 2 "I \ ' 5 [11‘ R113 N—- 11a H 1-T1 A A1'/ NoA4 ,N‘R’I A/ ‘4 0 A6 Q A2:A3)\( Az-‘A3 A-7 /N‘R1 The Al-A4, Bl-Bs, alkyl, Q, R1 and R11 radicals are each as defined above. U is, for e, bromine, iodine or triflate. Starting nds of the structure (A—l) (e.g. WO 99146, p. 75-76) and (A-7) (e.g. US 5,739,083 page 10, US 2003/187233A1, p. 6) are known or can be prepared by known s.
Compounds of the general structure (A—2) can be prepared in analogy to methods known from the literature from the compounds of the l structure (A—1) and carboxamide acetals (B-S) (e.g. , p. 50, Example 43; , p. 75-76). Compounds of the general structure (A-3) can be prepared in analogy to methods known from the ture from the compounds of the general structure (A-2) and hydrazine (e.g. , p. 50, Example 43; , p. 75-76). Compounds of the general structure (A—4) can be prepared in analogy to methods known from the literature from the compounds of the general structure (A—3) and (A—6) (e.g. , p. 50, \K’O 2015/067647 2014/073795 Example 44). Compounds of the general structure (A—5) can be ed in analogy to processes known from the literature by ester hydrolysis from compounds of the l structure (A-4) (see, for example, or WC 2010/133312). Inventive compounds of the general structure (I-Tl) can be prepared in analogy to peptide coupling methods known from the literature from the starting materials (A-5) and (A-7) (e.g. WO 51926 or ).
Process I-T2 The compounds of the structure (I-T2) can be prepared by the process specified in Reaction Scheme 2.
Reaction Scheme 2: .AIkyl R 0~Alky| N — B 3/82 ~ 2\ B1 / 33/ \ {:1 3| O O B 8 Bl\ BEES Z\B§ \ Rtth R", Rm. 3-1 / Hydrazine Ba/82‘B A1/ \‘ 0 1 R A .
I I "a TA3 3&3 O ‘Alkyl \ \ B Rub B-6 N‘N // 2‘81 83‘ \ 2‘ ‘ /N‘ A", Bd§35 NH A1. O — 8—4 AZ:A 3-3 R113 R11b ‘Alkyl NaOH /st /Bz~ B?/ '81 RM 1.Activation B?/ F1 Rm B \ 2' B \ 4\B —____—p 4\Br I \ R \ \ R11b J H 11h \ N‘N ,N‘R1 A Q 1-T2 A B‘5 At/ \4 0 A \II 0 A . MAN. 2A3 ‘ 3 OH N‘R‘I The A1 to A4, B1 to B5, alkyl, Q, R1 and R11 radicals are each as defined above. X is, for example, Cl, Br, I or a boronic acid or boronic ester radical. Starting compounds of the structure (B-l) (e.g. Filler, Robert; Kong, Zhengrong; Zhang, Zhaoxu; Sinha, Arun Kr.; Li, Xiaofang Journal of ‘WO 67647 — 109 — ne Chemistry, 80 (1996) p. 71 — 76; U82003/187233, p. 14, Example 21) and (B—6) are known or can be prepared by known methods.
Compounds of the general structure (B-2) can be prepared in analogy to methods known from the literature from the compounds of the l structure (3-1) and carboxamide acetals (B-8) (e. g. WO 2006/044505, Compound 60, Part A; , Intermediate 2). Compounds of the general ure (B-3) can be prepared in analogy to methods known from the literature from the compounds of the general structure (B-2) and hydrazine (e.g. , p. 50, Example 43; , be prepared in y to methods known from p. 75-76). Compounds of the general structure (3-4) can the literature from the compounds of the general structure (B-3) and (B-6) (e. g. , p. 50, Example 44, X = Br). Compounds of the l structure (B-S) can be prepared in analogy to ses known from the literature by ester hydrolysis from compounds of the general structure (B-4) (e.g. WO 2010/051926 or ). ive compounds of the general structure (I—Tl) can be prepared in analogy to peptide coupling methods known from the literature from the starting materials (13—5) and (13—7) (e.g. wo 2010/051926 or wo 2010/133312).
Stage 1 Dialkylaminoalkenylation ,Alkyl B RmkaOkal— B // 2‘B / B// 2781 83‘ \1 0 §\\ \ O BRBS "85 \ R111) R113 Rlla (13-1) (3-8) (3-2) Compounds of the general ure (B-2) can be prepared in analogy to methods known from the literature from the starting materials of the structure (B-1) and (B-8). The Bl-BS, alkyl and R11 ls are each as defined above. ng compounds of the structure (B-l) (e.g. Filler, Robert; Kong, Zhengrong; Zhang, Zhaoxu; Sinha, Arun KL; Li, Xiaofang Journal of Fluorine Chemistry, 80 (1996) p. 71 — 76; U82003/187233, p. 14, Example 21 [0294], USS739083, Example 6) are known or can be prepared by known methods. The reaction is conducted by reacting the compounds (B-l) with the compounds (B-8) under the conditions known in the literature for analogous reactions (6.g. EP1204323, p. 25, Example 13).
Stage 2 Pyrazole ring closure ‘ - llO — PCT/EPZUl4-/G73795 B? B.
BS// \ | o 33/ ‘ Hydrazine \ B4§Bs \ R111: ———> R113 B- (3'2) (3'3) Compounds of the general structure (B-2) can be prepared in analogy to methods known from the literature from the starting materials of the structure (B-2) and hydrazine. The Bl-B5 and R11 radicals are each as defined above. The preparation of the starting compounds of the structure (B-Z) is described above. The reaction is conducted by reacting the compounds (B-2) with hydrazine under the conditions known in the literature for ous reactions (EPl 382603, Example 3, p. 43) Stage 3 Aryl coupling A1/ A \4 O B B lib-AH 83% 2‘81 \ R B// 2 B1 O‘Alkyl BI l "a 3\ \ /N\NH 4\BS l\ R 8&8 N‘N 111) R11a R11b A1/ [3‘4 0 A2..A3)\( O‘Alkyl (B-3) (B-6) (B-4) nds of the general structure (B-4) can be prepared in analogy to methods known from the literature from the starting materials of the structure (B-3) and (B-6). The Al-A4, Bl—Bs, alkyl, R1 and R11 radicals are each as defined above. X is a c acid or a boronic ester radical. The preparation of the starting compounds of the structure (B-3) is bed above. The compounds of the general structure (B-6) are either commercially available or can be prepared by ses known to those skilled in the art. The reaction is conducted under the conditions known in the literature for analogous ons 9l40342, p. 96).
Stages 4, 5 Hydrolysis, amidation 83/8/ 2~ B1 R /BZ‘ | B/ B - _ B¢Bz.B | 11 a 3 x R 1. Activation 3 I 1 R BQB NaOH l 1‘s "a l Bl R11" "B,\ N-N ’ I\ R K35 \\ R .2 11b N‘N 11b H N‘N A/ A‘ R1 A‘/ A 0’ A 'A H \‘ 0 A1/ \4 O ‘Alkyl 2-/-\A 2 OH ,N‘Rl (B4) (B5) (B7) (I-T2) ‘ — 111 - Inventive nds of the general structure (I-TZ) can be prepared in y to peptide coupling methods known from the ture from the starting materials (B5) and (B7) [W02010- 051926; W02010-133312]. Compounds of the general structure (B5) can be prepared analogously to from compounds of the general structure (B4) processes known from the literature by ester hydrolysis [W02010—051926; w02010—133312]. The Al-A4, Bl-Bs, alkyl, Q, R1 and R" radicals are each as defined above. The preparation of the compounds of the ure (B-7) is described above.
Process I-T3 The compounds of the structure (I—T3) can be prepared by the process specified in Reaction Scheme 3a.
Reaction scheme 3a 82‘ / 2\B B3// B / \1 NH 853 y: N (R11ln ‘ 2 8% "t i7 BRBs N 4 _ H 35 Y-1 ,Alkyl \l/\ A4 83% 2 M B1 Bz‘B BI 11 B// 1 4\\B/lk (R )n 3\ N/ »\\ rN (R )n B\ \ 4\85 \—z Y-5 U A 0 An/ \4 Y-3 A2=A3 l 3&82‘3 B ? I 1 83¢ 2‘81 B \ /‘\ N/N (R11 "-Q | 4\85 )n B4\\B5AK R1, N/N (R11)n \ B-7 Y6 O ——————> _ A1/ \4 E, A/ A;1 O Ag—A3 OH 1‘ ’ < Aa—As_ 1-T3 ,N—Q The A1 to A4, B1 to B5, alkyl, Q, R1, n and R11 radicals are each as defined above. M is, for example, a boronic acid, boronic ester or trifluoroboronate. U is, for example, bromine, iodine or triflate. X is, for example, Cl, Br, I.
‘NO PLOTS/067647 ~ - i 12 Stage 1 Pyrazole Stage 1 of the preparation process for the inventive compounds (1 -T3): 82‘ 2‘13 Bf S: // 83‘ filN’N (R1111 .NH2 BRBS " BRBs \j Y-l Y—Z Inventive compounds of the general structure (Y-2) can be prepared in analogy to methods known from the literature from the starting materials of the structure (Y—l). The Bl-B5 and R11 radicals are each as defined above. Starting compounds of the structure (Y1) are known or can be prepared by known methods. Examples include [2,6-dichloro—4-(trifluoromethyl)phenyl]hydrazine, [3—chloro—5— (trifluoromethyl)pyridyl]hydrazine, [2,6—dichloro—4-[l ,2,2,2-tetraflu0ro-1 — (trifluoromethyl)ethyl]phenyl]hydrazine, [2,6—dimethyl—4-[l ,2,2,2—tetrafluoro-l — (trifluoromethyl)ethyl]phenyl]hydrazine, [2-methyl[1 ,2,2,2-tetrafluoro-l -(trifluoromethyl)ethyl] (trifluoromethyl)phenyl]hydrazine or [2-chloro[l ,2,2,2—tetrafluoro-l -(trifluoromethyl)ethyl]-6 - oromethyl)phenyl]hydrazine. They can be prepared, for example, by methods bed in US 2003/187233, p. 13; Haga, Takahiro et a1, Heterocycles, 22 (1984), p. 117-124.
Stage 2 Iodopyrazole Stage 2 of the ation process for the inventive compounds (1-T3): Bs// 2 \ [31 (R )n B//BZ\B1 \ N,N 3‘ \ ,N (Rll)n BRBS \_7 BRBS Ni? Y-2 Y—3 The B1-B5, n and R11 radicals are each as defined above. U is, for example, bromine or iodine.
The nds of the ural formula (Y-3) are, for e, l-(2,6-dichloro trifluoromethylphenyl)iodopyrazole, 3 -chloro(4-iodopyrazol—1 —yl) -5 —(trifluoromethyl)pyridine (CAS RN: 8611—89-2), l-(2,6-dichloro—4-heptafluor0isopropylphenyl)-4—iodopyrazole, l-(2,6-dimethyl— 4-heptafluoroisopropylphenyl)-4—iodopyrazole, l -[2—methyl[l ,2,2,2—tetrafluoro-l - (trifluoromethyl)ethyl] —6-(trifluoromethyl)phenyl]-4—iodopyrazole, 1—[2-chloro[1 ,2,2,2—tetrafluoro-l - (trifluoromethyl)ethyl](trifluoromethyl)phenyl]iodopyrazole or l-[2-ethyl-6—methyl[l,2,2,2- uoro(trifluoromethyl)ethyl]phenyl] —4-iod0pyrazole.
VVO 2015/067647 — 113 - Inventive nds of the general stlucture (Y—3) are prepared by reacting pyrazoles of the stmcture (Y-2) with halogenating agents. The B] to B5 and RI] radicals are each as defined above.
Suitable halogenating compounds are known to those skilled in the art, for example chlorine, bromine, iodine N—chlorosuccinimide, N—bromosuccinimide, N—iodosuccinimide, l ,3-dichlor0-5 ,5 - dimethylhydantoin, l,3-dibromo-5,5-dimethylhydantoin, sodium hypochlorite and iodine monochloride.
Preference is given to using bromine, iodine and iodosuccinimide. It may be ageous to conduct the reaction in the presence of an oxidizing agent, e.g. hydrogen peroxide. The reaction follows the conditions known from the literature, for e Guo Li et al., Tetrahedron Letters 48 (2007), 4595- 4599; Mary M. Kim et al., Tetrahedron Letters 49 (2008), 4026-4028.
Alternative coupling with pyrazole Alternatively, the compounds of the structure Y-3 can also be prepared by methods known from the literature through direct coupling of iodopyrazoles with appropriate aryl halides (e.g. Sammelson, Robert E. et al., J. of Organic try, 68 (2003), 8075—8079).
B—B 11 // 2 B1 //2 \1 HN,N (R )n 83‘ ,N (R11)n __, H _ B4—B5 aim/Z\ _ 5 (Y—8) (Y-9) (Y—3) The B1 to B5, n and R11 radicals are each as defined above. X is, for example, a halogen. U is, for e, bromine, iodine or e.
Starting compounds of the structure (Y-8) are known or can be prepared by known methods.
Examples include 2-brom0-1,3-dichloro[l,2,2,2-tetrafluoro-l-(trifluoromethyl)ethyl]benzene, 2- bromo-l ,3—dimethyl-5 -[l ,2,2,2—tetrafluoro—l uoromethyl)ethyl]benzene, 2-bromoethyl-3 -methyl[l ,2,2 ,2—tetrafluoro- l -(trifluoromethyl)ethy1]benzene, 2-bromo-1 -chloro-5 —[l ,2,2,2-tetrafluoro-1 - (trifluoromethy1)ethyl] —3 -(trifluor0methyl)benzene, 2-bromo-l -methyl-5 -[l ,2,2,2—tetrafluoro-l - (trifluoromethyl)ethyl]—3 uoromethyl)benzene, 2-bromo- l o-5 - [1 ,2,2,2—tetrafluoro-l - (trifluoromethyl)ethyl] ~3 u0romethoxy)benzene, o-l -methyl—5 — [l ,2,2,2-tetrafluoro-l - (trifluoromethyl)ethyl](trifluoromethoxy)benzene. They can be prepared, for example, by the methods described in EP1253128, pages 8-10.
Stage 3 Boronic acid coupling Stage 3 of the preparation s for the inventive compounds (l—T3): — 114 — B// 2~ B ,Alkyl 3 1 O | l B" // 2 B A B4\\ )\ ,N (Run 83‘ \1 (R1|)n A? 3| 0 B5 N 8% N,N \ 4 \—2 + A1\ YA4 B5 A, O U M A/ \ A2=A3 O-Alkyl (Y-3) (Y-4) (Y-5) The A1 to A4, B1 to B5, alkyl, n and R11 radicals are each as defined above. U is, for e, bromine, iodine or triflate when M is a boronic acid, boronic ester or trifluoroboronate; or U is, for e, a boronic acid, boronic ester or trifluoroboronate when M is bromine, iodine or triflate.
Inventive compounds of the general structure (Y-5) can be prepared by methods known from the literature, by means of palladium—catalysed reactions from the co-reactants (Y-3) and (Y-4) (e.g. WO 2005/040110 or ). The nds of the general ure (Y—4) are either commercially available or can be prepared by processes known to those skilled in the art.
Stages 4, 5 Hydrolysis, amidation / 2\ / 2\ B B./ B BT/ 3 IB1 Bf ? H 1 ,N-Q 8' k 11 11 B' A'31 R1 4\\ ,N B \ k w (R ) (R B7 N n "\35 - N’ )" QB, N’N (R )" \ —> \ ——-—> ._A‘1 O A4 0 A4 0 A1/ ‘ A" \ A/ \ ‘A2=A3 N-Q A,=A3 O-Alkyl A2=A3 OH R1 (Y-5) (Y—6) (I-T3) Inventive compounds of the general ure (I-T3) can be prepared in analogy to peptide coupling methods known from the literature from the starting materials (Y~6) and (Y—7) (e.g. WO 2010/051926 or ). Compounds of the l ure (Y—6) can be prepared in analogy to processes known from the literature by ester hydrolysis from compounds of the general structure (Y-5) (e.g. or ). The A1 to A4, B1 to B5, alkyl, Q, R1 and R11 radicals are each as defined above.
Stage 3 alternative: Coupling with amides Alternatively, the inventive compounds (I-T3) can be prepared by general preparation process ‘ — 115 - Reaction scheme 3b / 2\ B R1\N,Q Bcls/ ['31 B// 2\ByN’ijwn1 A Bd\ A\ /N (R11) n 3‘ A? 31 0 BS N\ Bd§BS + A1 YAII ——‘> A, 0 U M A / \ Aan ,N—Q (Y-3) (Y-10) (I-T3) The A1 to A4, B1 to B5, alkyl, Q, R1, n and R11 radicals are each as defined above. U is bromine, iodine or triflate when M is a boronic acid, boronic ester or roboronate. U is a boronic acid, boronic ester or trifluoroboronate when M is bromine, iodine or triflate.
Inventive compounds of the general structure (I-T3) can be prepared by methods known from the literature, by means of palladium-catalysed reactions from the ctants (Y-3) and (Y-10) (e.g. or ). The compounds of the general structure (Y-10) are either commercially available or can be prepared by processes known to those skilled in the art. The preparation of nds of the structure (Y-3) has already been described above.
Process I-T4 The compounds of the structure (I—T4) can be prepared by the process specified in Reaction Scheme 4.
Vx’O 2015/067647 — ll6 - PCT/EPZGl4/O73795 on Scheme 4 / BARB B 85/ \1 tert—Butylnitrite/CuCI2/1,1—Dichloroethylene B/ 3\B1 3‘ §B)‘NH2 \ 4%5 DMF—Acetal 8» / ExZ‘B B? \B1 Hydrazine Ba‘/ 1 \ N/ \ / /_NH .— B4§Bs \ B4§B N N O B?.\ B B1 B7/_"\\ N aOH 3%," D-6 JewA’AS 1 Activation BfBZ\B1‘ Q'H‘ R1 BS IZBT 1—T4 A':2-‘A:‘\(O Q-N‘R1 The A1 to A4, B1 to B5, alkyl, Q and R1 radicals are each as defined above. X is Cl, Br, I.
Starting compounds of the structure (D-l) (e.g. EP2319830, p. 330) and (D-7) are known or can be prepared by known methods.
The ons can be conducted by the processes described in the literature, for example WC 2012/149236, Majumder, Supriyo et al., Advanced sis and Catalysis, 351 (2009), 2013-2023, or US 5,061,705.
VVO 2015/067647 - 117 — 95 Compounds of the general structure (D2) can be prepared in analogy to methods known from the literature from the compounds of the general structure (D1) (e.g. W02008148868A1, p. 87).
Compounds of the general structure (D3) can be prepared in analogy to reactions known from the ture from the nds of the general structure (D2) and an iminium salt (e.g. Knorr, Rudolf; Loew, Peter; Hassel, Petra; Bronberger, Hildegard Journal of Organic Chemistry, 49 (1984) p. 1288- 1290). Compounds of the general structure (D4) can be prepared in analogy to methods known from the literature from the compounds of the general structure (D3) and hydrazine (e.g. 080969 A1, p. 102-103, Example 104). Compounds of the general structure (D5) can be prepared in y to s known from the literature from the compounds of the general structure (D4) and (D7) (e.g.
W02013009791, p. 50, Example 44). Compounds of the general structure (D6) can be prepared analogously to processes known from the literature by ester hydrolysis from compounds of the l structure (D5) [W02010-051926; W02010-133312]. Inventive nds of the general ure (1- T4) can be prepared in analogy to peptide coupling methods known from the ture from the starting materials (D6) and (D8) [W02010-051926; W02010-133312]. id="p-342" id="p-342" id="p-342" id="p-342" id="p-342" id="p-342"
[342] The compounds of the structure (I-T4) can alternatively be prepared by the process specified in Reaction Scheme 5.
VVO 20‘15/067647 2014/073795 Reaction Scheme 5: A? R11 \[fifl\ A2:A)\(O + KEQ\ .N /B2—B1 1. i-PropylMgCI/LiCI B/ /Bz"‘ B1 0 3 Pd(0) \ >—x 2 B< >—Bb:é 327-35 \ ,o BFBs O‘B‘ O D-10 B/ 32 ‘B‘ I I R11 4% \IN N OHa '35 \ 0-6 At/ \4 O Az‘Aa OH 1, Activation ¢Bik -H‘R1 8? [B1 Q B‘\\ 3-7 Bs \ \N The A1 to A4, B1 to B5, alkyl, Q, R1 and R11 radicals are each as defined herein. X is Cl, Br, 1. ng compounds of the structure (D-7), (D-9) and (D-ll) (e.g. EP1253128, p. 8-10) are known, and some are commercially available or can be prepared by known methods.
The reactions can be conducted by the processes described in the literature: Stage 1 Pyrazole coupling Stage 1 of the preparation process for the inventive compounds (I-T4): \VO 2015/0’67t’47 - 119 — PCT/EPZOl4/073795 O‘Alkyl 1, \ m H A2:A3 D-7 A'ky' 0-11 0-9 Compounds of the l structure (D-9) can be prepared in y to methods known from the literature from the starting materials of the structure (D-7) and (D-ll). The Al-A4, alkyl and X radicals are each as defined above. Starting nds of the structure (D-7) are known (e.g.
W02004099l46Al, p. 68-69) or can be prepared by known methods. Examples e: methyl 2- chloro-S-iodobenzoate, ethyl 2-bromoiodobenzoate, methyl 5-bromo—2-chlorofluorobenzoate, ethyl 5-bromo—2—chloronicotinate. The starting compounds of the structure (D-ll) are known, and some of them are commercially available or can be prepared by known methods. Examples include 4— bromopyrazole, 4-bromo-3~methylpyrazole, 4—bromo—3,5-dimethylpyrazole and o (trifluoromethyl)pyrazole.
The as yet unknown compounds (D—9) can be prepared in analogy to known processes for joining pyrazoles to aromatic systems (e.g. W02013009791, p. 50, Example 44).
Pyrazole alternative preparation id="p-348" id="p-348" id="p-348" id="p-348" id="p-348" id="p-348"
[348] Alternatively, the inventive compounds of the general structure (D9) can be obtained via the route ed in Reaction Scheme 6.
Reaction Scheme 6: HzN‘N A1/ ’0‘": O A1/ HO A2:A3)\f. + ———-> A2:A3 O‘Alkyl O‘Alkyl D-13 D-14 RIM R11a ‘ H x \ l \.N \ N.N R1") *—————‘ R11b A1/ MOA A1: HO A2:A3 2A3 O‘Alkyl Alkyl D-15 "’0 2015/067647 - 120 — 2014-/073795 The A] to A4, alkyl and R11 radicals are each as defined above. X is Cl, Br, 1. Starting compounds of the structure (D—13) are known (e.g. WO2004099146A1, p. 68—69) or can be prepared by known methods. Examples include: methyl 5-amino-2—chlorobenzoate, ethyl 5—amino-2—chlorobenzoate, methyl 5~aminochlorofluorobenzoate, ethyl 5-aminochloronicotinate.
The as yet unknown compounds (D-14) can be prepared in analogy to known processes for preparing aryl hydrazines (e.g. WO 2004058731, p. 65).
Inventive compounds of the general ure (D-15) can be prepared in analogy to methods known from the ture from the starting als of the structure (D-14). The A1 to A4, alkyl and R11 radicals are each as defined above. Starting compounds of the structure (D-14) are known or can be prepared by known methods. Examples include methyl ro-5 zinobenzoate, ethyl 2—chloro hydrazinobenzoate, methyl 2—chloro—3-fluorohydrazinobenzoate, ethyl 2—chloro hydrazinonicotinate. The reaction can be conducted analogously to the ions for pyrazole ring closure known in the literature (e.g. Sachweh, Volker; Langhals, Heinz Chemische te, 119 (1986) 1627-1639). id="p-352" id="p-352" id="p-352" id="p-352" id="p-352" id="p-352"
[352] Inventive nds of the general structure (D9) are prepared by reacting pyrazoles of the structure (D—15) with halogenating agents. The A1 to A4, alkyl and R11 radicals are each as defined above. Preferred compounds of the structure (D15) e methyl 2-chloro(pyrazol—1—yl)benzoate, ethyl 2-chloro—5-(pyrazolyl)benzoate, methyl 2-chlorofluoro(pyrazol-l-yl)benzoate, ethyl 2- chloro(pyrazol-l -yl)—nicotinate. id="p-353" id="p-353" id="p-353" id="p-353" id="p-353" id="p-353"
[353] Suitable halogenating compounds are known to those skilled in the art, for e e.g. chlorine, bromine, iodine, N—chlorosuccinimide, osuccinimide, N—iodosuccinimide, 1,3-dichloro- ,5-dimethylhydantoin, 1,3-dibromo—5,5-dimethylhydantoin, sodium hypochlorite and iodine monochloride. Preference is given to using bromine, iodine, bromosuccinimide and iodosuccinimide. It may be advantageous to conduct the reaction in the presence of an oxidizing agent, e.g. hydrogen peroxide. The reaction follows the conditions known from the ture, for example Guo Li et al., Tetrahedron Letters 48 (2007), 4595—4599; Mary M. Kim et al., Tetrahedron Letters 49 (2008), 4026- 4028.
Stage 2 Boronic ester [3 54] Stage 2: Preparation of the starting compounds of the structure (D12) B—B 1-Mg 8—8 B// 2 1 1 >—x B// 2 .o\ >—B A'ky' 3\B—B 2. o—Alkyl 'Mk. 3\B—B 4— 5 yb_ .O‘Alkyl 4— 5 Alkyl VVO 67647‘ - 121 — PCT/EPZGI4/07379‘S (Y-S) (D-16) (D-12) Inventive compounds of the general structure (D—12) can be ed in analogy to methods known from the ture (Chien, Yuh-Yih; Chou, Meng-Yen; Leung, t; Liao, Yuan—Li; Lin, Chang-Chih; Wong, Ken—Tsung; Journal of Organic Chemistry, 67 (2002) p. 1041-1044) from the starting materials of the structure (D-lO) through reaction with magnesium and subsequent reaction with boric esters of the structure (D-16).
The Bl-Bs and alkyl radicals are each as defined above.
The boric esters of the structure (D-13) used in the reaction are known or can be prepared by known methods. es include trimethyl borate, triethyl borate and 2-methoxy-4,4,5,5—tetramethyl- 1,3,2-dioxaborolane.
Alternatively, the inventive nds of the general structure (D-12) can be prepared in analogy to methods known from the literature (Tang, Wenjun; eddy, Santosh; Zhang, Yongda; Wei, Xudong; Savoie, Jolaine; Patel, Nitinchandra D.; Yee, Nathan K. ; Senanayake, Chris H.; Organic Letters, 13 (2011) S. 1366-1369) from the starting materials of the structure (D-10) through reaction with nes of the structure (D-14) in the presence of catalysts.
Alkyl—Q ,O~Alky| B— B 82-31 Alkyl~o' 'o—Alkyl 32—31 B! 0‘ Ba/ Akyl ‘ >—X ‘ >—B' _ b—Alk _ yI B4— B5 Catalyst B4— 85 (Y-8) (D—17) (D-12) id="p-359" id="p-359" id="p-359" id="p-359" id="p-359" id="p-359"
[359] The boric esters of the structure (D-17) used in the on are known or can be prepared by known methods. Examples include 4,4,5,5-tetramethyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2—yl)— 1,3,2-dioxaborolane (bis(pinacolato)diboron).
Catalysts used may, in particular, be compounds and complexes of palladium and Cu(I).
VVO 2015/067647 — 122 — Stage 3 Aryl coupling R118 83% 2‘81 X I R113 \\ N B B Bl 2— 1 4% s \ N Alkyl 85 \ .N "b 83/ >_B. R \B—B N / A4 o Alkyl R A‘ O 11b \ E— 5 / A4 A2:A A1_ \ O 3 o A- M ‘Alkyl 2-A3 0~Amw (13-9) ) (D-5) Inventive nds of the general structure (D—S) are prepared by reacting the compounds of the structure (D—9) with boronic esters of the structure (D—12).
The Al-A4, Bl-BS, R11, alkyl and X radicals are each as defined above.
The preparation of the compounds of the ures (D-9) and (D-12) is described above.
Examples of compounds of the structure (D—9) include: methyl 5-(4-bromopyrazol—l-yl) chlorobenzoate, methyl 5—(4—iodopyrazol—1-yl)chlorobenzoate, ethyl 5-(4-bromo—3-methylpyrazol yl)chlorobenzoate, methyl 5-(4-bromo—3—(trifluoromethyl)pyrazolyl)chlor0benzoate, methyl 5- (4-bromo—3-(trifluoromethyl)pyrazolyl)chlorobenzoate, methyl 5-(4-bromo-3,5-dimethy1pyrazol- 1-yl)chlorobenzoate and ethyl 5-(4-bromomethylpyrazol-1 —y1)chloronicotinate.
The reaction is conducted under the conditions described in the literature, for example WO 2005040110 or WO 2009089508.
Stages 4, 5 Hydrolysis, amidation 3 1 R B3/ 2‘8 R 8' I 11- l 113 R35 \ BI\ N 1. Activation \SB Rub 1|b A 4 A2:A3H0 ~R1 _ Q- A|/'A3)\€OA'z O‘Nkyl Q-N‘R1 (13-5) (13-6) (D-8) (1-T4) Inventive compounds of the general structure (I-T4) can be prepared in analogy to peptide coupling s known from the ture from the starting materials (D-6) and (D-8) [W02010051926; W02010133312]. Compounds of the general structure (D-6) can be prepared ously to processes known from the literature by ester hydrolysis from compounds of the general VVO 2015/067647 - 1 [Q U) r PCT/E132014/073795 structure (D—S) [WO2010—051926; W02010133312]. The AI-A4, Bl-BS, alkyl, Q, R] and R11 ls are each as defined above. The preparation of the compounds of the ure (D5) is described above.
(I-T5): Compounds of the formula (I—T5) can be prepared, for example, analogously to Friedrich, L.E. et al. Journal of Organic Chemistry, 43 (1978), 34—38; or Huettel, R. et a1. che Berichte, 93 , p. 1425-1432; or Sato, T et al., Bulletin of the Chemical Society of Japan, 41 (1968), p. 3017-3018.
(I-T8): Compounds of the formula (I-T8) can be prepared, for example, analogously to EP 1 405 636, Example 5; or EP 2 301 538, p. 162; or Schmidt, Bernd et al., an Journal of Organic try, (2011), p. 4814-4822. id="p-369" id="p-369" id="p-369" id="p-369" id="p-369" id="p-369"
[369] (I-T9): Compounds of the formula (I—T9) can be prepared, for example, analogously to Ma, Shengming et al., Chemistry-A European Journal, 9 (2003), p. 2447-2456.
(I—T10): Compounds of the formula (I—T10) can be ed, for example, analogously to EP 2 301 538, p. 162.
(I-T1 1): Compounds of the formula (I-Tl 1) can be prepared, for example, analogously to EP 2 301538, p. 165.
(I—T12): Compounds of the formula (I-T12) can be prepared, for example, analogously to EP 2 301538, p. 164. ): nds of the formula (I-T13) can be prepared, for example, analogously to EP 2 301538, p.164. id="p-374" id="p-374" id="p-374" id="p-374" id="p-374" id="p-374"
[374] (I-Tl4): Compounds of the formula (I-T14) can be ed, for example, analogously to Hibi, Shigeki et al., Bioorganic & Medicinal Chemistry s, 10 (2000), p. 623—626 or Wang, Xiang et al.
Journal of c Chemistry, 72 (2007), 1476—1479; EP1405636, page 31.
(I—T15): Compounds of the formula (I-T15) can be prepared, for example, analogously to Chattopadhyay, Buddhadeb et al., Organic Letters, 13 (2011), p. 3746-3749. id="p-376" id="p-376" id="p-376" id="p-376" id="p-376" id="p-376"
[376] (I—T16): Compounds of the formula (I—T16) can be ed, for example, analogously to Campi, Eva M. et a1. Tetrahedron Letters, 32 (1991), p. 1093-1094; or on, Benjamin B. et al., Organic Letters, 13 (2011), p. 3289—3291; or Kloetzel et al. Journal of the American Chemical Society, 79 , p. 4222; or Chi, Yonggui Robin et al., Journal of the American Chemical Society, 135 (2013), p. 8113-8116. id="p-377" id="p-377" id="p-377" id="p-377" id="p-377" id="p-377"
[377] (I-T18): Compounds of the formula (I—T18) can be prepared, for example, analogously to EP 2 311 455, p. 150; or Balaban, A.T. et al. Tetrahedron, 19 (1963), p. 2199—2207.
V70 2015/067647 — 124 — (l-Tl9): nds of the formula (I-Tl9) can be prepared, for example, analogously to WO 2004/14366, p. 108.
(I—T20): Compounds of the formula (I-T20) can be prepared, for example, analogously to Araki, Hiroshi; Katoh, Tadashi; Inoue, Munenori; Synlett, (2006), p. 555-558; US 6,545,009, p. 27, Example 1.
(I-T21): Compounds of the formula (I-T21) can be ed, for example, ously to WO 2004/72050, p. 13; or US 6,545,009, p. 27.
Process I—T22 The compounds of the structure (I-T22) can be prepared by the process specified in Scheme 7. on Scheme 7: B x B 2 B ~ \ / BREE BRBS \\ nating agent A1/ A\4 Az‘AH0 O‘Alkyl 3/32‘81 3, \ N‘OH B4§B Base 5 X 1, Activation The Al-A4, Bl-Bs, alkyl, Q, R1 and R11 radicals are each as defined above. X is Cl, Br, 1. Starting compounds of the structure (W-l) and (W-6) are known (W1 e.g. US 2011/53904 p. 19, W6 e.g. WO VVO? 20157067647 - l [J ‘JI l E’CT/EPZOl4/G73795 2012/175474, p. 117-118) or can be prepared by known s. The reactions are conducted analogously to the conditions specified for ation of the nds (I—T23).
Stage 1 de Stage 1 of the preparation process for the inventive compounds (I-T22): // 2‘3 / 2 B 83‘ \1 __> 833/ \1 /o \ X (W1) (W2) Inventive nds of the general structure (W2) can be prepared in analogy to methods known from the literature (USS739083, Example 2; W02011/23667, p. 34) from the starting materials of the structure (W1).
The Bl-B5 and X radicals are each as defined above. X is, for example, chlorine, bromine or iodine.
Starting compounds of the structure (B1) are known or can be prepared by known s.
Examples include 2-bromo-l,3—dichlor0[1,2,2,2—tetrafluor0-l-(triflu0r0methyl)ethyl]benzene, 2- bromo-l ,3 -dimethyl—5 -[l ,2,2,2-tetrafluoro-l -(trifluoromethy1)ethyl]benzene, 2—bromo—1 -3 -methyl- - [l ,2,2,2-tetrafluoro-1 -(trifluor0methyl)ethyl]benzene, 2-br0mo—l ~chloro[1,2,2,2-tetraflu0ro—l— (trifluorornethyl)ethyl] —3 -(trifluoromethyl)benzene, 2—bromo-l -methyl-5 - [l ,2,2,2-tetrafluoro-l — (trifluoromethyl)ethyl]-3 -(trifluoromethyl)benzene, 2-bromo-1 -chloro-5 -[1 ,2,2,2-tetrafluor0-1 - (trifluoromethyl)ethyl] -3—(trifluoromethoxy)benzene, 2-bromo-1 -methyl—5—[l ,2,2,2-tetrafluoro (trifluoromethyl)ethyl] -3 —(trifluoromethoxy)benzene, l ,3 -dimethyliodo-5 -[ l ,2,2,2-tetraflu0ro-l - (trifluoromethyl)ethyl]benzene, 2—i0do—l -methyl-5 - [l ,2,2,2-tetrafluor0-l -(trifluoromethy1)ethyl] -3 - (trifluoromethyl)benzene. They can be prepared, for example, by the methods bed in EP1253128, pages 8—10.
Stage 2 Oxime [3 87] Stage 2 of the preparation process for the inventive compounds (1-T22): Br B B// ‘\B1 - H2NOH B// 81 3‘ )VO —> 3‘ »\//N‘OH BRBS B4§B5 ‘NO- ZOE/067647 — 126 — Inventive compounds of the general stmcture (W3) can be prepared in analogy to methods known from the literature from the staiting materials of the structure (W2). The Bl-Bs radicals are each as defined above. The preparation of the starting nds of the structure (W2) is described above.
Examples include 2,6-dichloro[l,2.,2,2-tetrafluoro-l~(trifluoromethyl)ethyl]benzaldehyde, 2,6- dimethyl—4-[l ,2,2,2-tetrafluoro-1 -(trifluoromethyl)ethyl]benzaldehyde, l-6—methyl-5 -[1 ,2,2,2- tetrafluoro(trifluoromethy1)ethyl]benzaldehyde, 2-chloro [ 1 ,2,2,2—tetrafluoro-l - (trifluoromethyl)ethyl]—6—(trifluoromethyl)benzaldehyde, 2-methyl[l ,2,2,2—tetrafluoro-l - oromethyl)ethyl] (trifluoromethyl)benzaldehyde, 2—chloro[l -tetrafluoro-l - (trifluoromethyl)ethyl] —6-(trifluoromethoxy)benzaldehyde, 2-methyl-4—[l ,2,2,2-tetrafluoro-l - (trifluoromethyl)ethyl](trifluoromethoxy)benzaldehyde. The preparation thereof is described above.
The compounds of the structural fonnula (W3) are novel. The as yet unknown compounds (W3) can be prepared in analogy to the known ses for preparing oximes from aldehydes (H. Metzger in Houben—Weyl, volume X/4, page 55 ff, Georg Thieme Verlag Stuttgart 1968). The compounds of the structural formula (W3) may be in the form of pure stereoisomers, but also in the form of es of the stereoisomers.
Stage 3 Hydroxamyl chloride Stage 3 of the preparation s for the inventive nds (1—T22): B// B1 83/ $1 Halogenating agent B \ LN‘OH 3R8HNSOH 4\ 85 5 X (W3) (W4) Inventive compounds of the general structure (W4) are prepared by reacting the oximes of the structure (W3) with halogenating agents. id="p-392" id="p-392" id="p-392" id="p-392" id="p-392" id="p-392"
[392] The Bl—B5 radicals are each as defined above. X is chlorine, bromine or iodine.
Typical compounds of the structure (W4) are, for example, 2,6-dichloro[1,2,2,2—tetrafluoro— 1 —(trifluoromethyl)ethyl] -N—hydroxybenzimidoy1 chloride, 2,6-dimethyl[1 ,2,2,2—tetrafluoro—l — (trifluoromethyl)ethyl]—N-hydroxybenzimidoyl chloride, 2-ethyl—6—methyl-5—[l,2,2,2—tetrafluoro-1— (trifluoromethyl)ethyl] —N—hydroxybenzimidoyl chloride, 2—chloro[l -tetrafluoro—l - (trifluoromethyl)ethyl] (trifluoromethyl)-N-hydroxybenzimidoyl chloride, 2-methyl[l ,2,2,2- tetrafluoro—l-(trifluoromethyl)ethyl](trifluoromethyl)-N-hydroxybenzimidoyl chloride, 2—chloro ,2—tetrafluoro—1—(trifluoromethyl)ethyl]-6—(trifluoromethoxy)—N—hydroxybenzimidoyl chloride, 2~ ‘NO 2015/067647 — 127 — 2014/073795 methyl-4—[l ,2,,2 ,E—tetra fluoro—l -(trifluoromethyl)ethyl] —6 luoromethoxy) —l\E —hydroxybenzimidoyl chloride, 2 -methyl—4—[l ,2,2,2—tetrafluoro-l —(trifluormnethyl)ethyl] —6-(trifluoromethyl)—N- hydroxybenzimidoyl bromide.
Suitable halogenating compounds are known to those skilled in the art, for example chlorine, bromine, iodine, N—chlorosuccinimide, osuccinimide, N—iodosuccinimide, l,3—dichloro-5,5- dimethylhydantoin, 1,3-dibromo-5,5~dimethylhydantoin, benzyltrimethylammonium tetrachloroiodate and sodium hypochlorite. Preference is given to using chlorinating reagents.
The reaction can be conducted using le ts.
Useful ts or solvents for conducting the processes according to the invention in principle include all organic solvents which are inert under the specific reaction conditions. Examples include: hydrohalocarbons (e.g. hydrochlorocarbons, such as tetraethylene, hloroethane, dichloropropane, methylene chloride, dichlorobutane, form, carbon tetrachloride, trichloroethane, trichloroethylene, pentachloroethane, difluorobenzene, 1 ,2-dichloroethane, chlorobenzene, bromobenzene, dichlorobenzene, chlorotoluene, trichlorobenzene), alcohols (e.g. ol, ethanol, panol, butanol), ethers (e.g. ethyl propyl ether, methyl tert-butyl ether, n—butyl ether, anisole, phenetole, cyclohexyl methyl ether, dimethyl ether, diethyl ether, dipropyl ether, diisopropyl ether, di-n—butyl ether, utyl ether, diisoamyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, dichlorodiethyl ether and polyethers of ethylene oxide and/or propylene oxide), amines (e.g. trimethyl-, triethyl-, tripropyl—, tributylamine, N—methylmorpholine, pyridine and tetramethylenediamine), nitrohydrocarbons (e.g. nitromethane, nitroethane, nitropropane, nitrobenzene, chloronitrobenzene, o— nitrotoluene; es such as acetonitrile, propionitrile, butyronitrile, isobutyronitrile, benzonitrile, m- chlorobenzonitrile), tetrahydrothiophene dioxide, yl sulphoxide, ethylene sulphoxide, yl sulphoxide, benzyl methyl sulphoxide, diisobutyl sulphoxide, dibutyl sulphoxide, diisoamyl sulphoxide, sulphones (e.g. dimethyl, diethyl, dipropyl, dibutyl, diphenyl, dihexyl, methyl ethyl, ethyl propyl, ethyl isobutyl and pentarnethylene sulphone), aliphatic, cycloaliphatic or aromatic hydrocarbons (e.g. pentane, hexane, heptane, octane, nonane and technical arbons), and also what are called "white spirits" with components having boiling points in the range from, for example, 40°C to 250°C, cymene, petroleum fractions within a boiling range from 70°C to 190°C, cyclohexane, methylcyclohexane, petroleum ether, n, octane, benzene, toluene, chlorobenzene, enzene, nitrobenzene, xylene, esters (e.g. methyl, ethyl, butyl and yl acetate, dimethyl, dibutyl and ethylene carbonate); amides (e.g. hexamethylenephosphoramide, forrnamide, N—methylforrnamide, N,N- dimethylformamide, N,N—dipropylformamide, N,N-dibutylformamide, N—methylpyrrolidine, N- methylcaprolactam, l ,3 -dimethyl—3 ,4, 5 ,6-tetrahydro-2( 1 H)-pyrimidine, octylpyrrolidone, octylcaprolactam, l,3-dimethyl-2—imidazolinedione, N—formylpiperidine, N,N’—1,4-diformylpiperazine) and ketones (e. g. acetone, acetophenone, methyl ethyl ketone, methyl butyl ketone).
\WO 67647 — 128 — 2014/073795 Prefen'ed diluents used may be any solvent that does not impair the reaction, for example water.
Useful examples are aromatic hydrocarbons such as benzene, toluene, xylene or chlorobenzene; halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane or carbon tetrachloride, open-chain or cyclic ethers such as diethyl ether, dioxane, tetrahydrofuran or 1,2- dimethoxyethane; esters such as ethyl acetate and butyl acetate; ketones, for example acetone, methyl isobutyl ketone and cyclohexanone; amides such as ylformamide and dimethylacetamide, N- methylpyrrolidone; nitriles such as acetonitrile or propionitrile; and other inert solvents such as 1,3- dimethy1imidazolidinone; the solvents may be used alone or in a combination of 2 or more.
The reaction can be executed within a wide temperature range. Usually, it is conducted within a temperature range from -78°C to 200°C, preferably at temperatures between —10 and 150°C. The reaction can be executed under elevated or else reduced re. But it is preferably conducted under rd pressure. The reaction times are between 0.1 and 72 hours, preferably n 1 and 24 hours.
To perform the reaction, 1 to 3 mol, preferably 1 to 1.5 mol, of halogenating agent are used per mole of the compound of the structure (W3) in a solvent, for example dimethylformamide (DMF).
Stage 4 Ring closure Stage 4 of the preparation s for the inventive compounds (1-T22): 8/3243, \ /N‘OH Bi::Bs X A2:AH0 3 OeAmw (W4) (W8) (W5) ive compounds of the general structure (W5) are prepared by reacting the hydroxamyl chlorides of the structure (W4) with acetylenes of the structure (W8).
The Al-A4, B1-B5, R11 and alkyl radicals are each as defined above. X is halogen, such as chlorine, bromine, iodine.
The preparation of the nds of the structure (W4) is described above. Typical nds of the structure (W4) are, for example, 2,6-dichloro[1,2,2,2-tetrafluoro(trifluoromethyl)ethyl]~N- hydroxybenzimidoyl chloride, 2,6—dimethyl—4-[1 ,2,2,2—tetrafluoro—1 -(trifluoromethy1)ethyl]-N- hydroxybenzimidoyl de, 2-ethy1—6—methy1[1,2,2,2-tetrafluoro(trifluoromethy1)ethy1]—N— WC 2015/067647 - 129 — hydroxybenziniidoyl chloride, 2—chloro-4—[l ,2,2,2—tetrafluoro—l -(irifluorometl‘ryl)ethyl] ~6— (trifluorornethyl)-N—hydroxybenzimidoyl chloride, 2—inethyl [1 ,2,2,2-tetrafluoro—l — (trifluoromethyl)ethyl]-6—(trifluorornethyl)-N—hydroxybenzi1nidoyl chloride, 2-chloro[1,2,2,2— tetrafluoro—l -(trifluoromethyl)ethy1](trifluoromethoxy)-N-hydroxybenzimid0yl chloride, 2-methyl [1 ,2,2,2-tetrafluoro(trifluoromethyl)ethyl]—6-(trifluoromethoxy)—N-hydroxybenzimidoyl chloride, 2— 1nethy1 [1 ,2,2,2-tetrafluoro-1 -(trifluoromethyl)ethyl]—6-(trifluor0methyl)-N-hydroxybenzimidoyl bromide.
The compounds of the structure (W8) are known (WO2012107434, p. 103) or can be prepared by methods known from the literature (Chinchilla, Rafael; Naj era, Carmen, Chemical Society Reviews (2011), 40(10), 5084-5121, Chinchilla, Rafael; Najera, , Chemical s (Washington, DC, United States) (2007), 107(3), 874—922). Typical compounds of the structure (W8) are, for example, methyl 2-chlor0-5—ethynylbenzoate, ethyl 2-bromo—5-ethynylbenzoate, methyl 2-chloroethynyl fluorobenzoate, ethyl ro-5 -ethyny1nicotinate, ethyl 5—ethynylmethy1nicotinate.
The reaction can be conducted using suitable solvents. id="p-406" id="p-406" id="p-406" id="p-406" id="p-406" id="p-406"
[406] Useful diluents or ts for conducting the processes according to the invention in principle include all organic solvents which are inert under the specific reaction conditions. Examples include: hydrohalocarbons (e.g. hydrochlorocarbons, such as tetraethylene, tetrachloroethane, dichloropropane, methylene chloride, dichlorobutane, chloroform, carbon tetrachloride, trichloroethane, trichloroethylene, pentachloroethane, difluorobenzene, 1 ,2—dichloroethane, chlorobenzene, enzene, dichlorobenzene, chlorotoluene, trichlorobenzene), ls (e.g. methanol, ethanol, isopropanol, butanol), ethers (e.g. ethyl propyl ether, methyl tert-butyl ether, n-butyl ether, anisole, phenetole, cyclohexyl methyl ether, dimethyl ether, diethyl ether, yl ether, diisopropyl ether, di-n—butyl ether, diisobutyl ether, diisoamyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, dichlorodiethyl ether and polyethers of ne oxide and/or propylene oxide), amines (e.g. trimethy1-, triethyl—, tripropyl-, tributylamine, N-methylmorpholine, pyridine and tetramethylenediamine), nitrohydrocarbons (e.g. nitromethane, nitroethane, nitropropane, nitrobenzene, nitrobenzene, o- nitrotoluene; nitriles such as acetonitrile, propionitrile, butyronitrile, isobutyronitrile, benzonitrile, m- benzonitrile), tetrahydrothiophene dioxide, dimethyl sulphoxide, tetramethylene sulphoxide, dipropyl sulphoxide, benzyl methyl xide, diisobutyl sulphoxide, dibutyl xide, diisoamyl sulphoxide, nes (e.g. dimethyl, diethyl, yl, dibutyl, diphenyl, dihexyl, methyl ethyl, ethyl propyl, ethyl isobutyl and ethylene sulphone), aliphatic, cycloaliphatic or aromatic hydrocarbons (e.g. pentane, hexane, heptane, octane, nonane and technical arbons), and also what are called "white spirits" with components having boiling points in the range from, for example, 40°C to 250°C, cymene, petroleum fractions within a boiling range from 70°C to 190°C, cyclohexane, methylcyclohexane, petroleum ether, n, , benzene, toluene, chlorobenzene, bromobenzene, nitrobenzene, xylene, esters (e.g. methyl, ethyl, butyl and isobutyl acetate, dimethyl, dibutyl and ‘ ethylene carbonate); amides (eg. hexamethylenephosphoramide, forniamide, N—methylformainide, N,N— ylfonnamide, N,N-dipropylformamide, butylformamide, N—methylpyrrolidine, N- methylcaprolactam, 1 ,3-dimethyl—3 ,4,5 ,6-tetrahydro-2(1H)-pyrimidine, octylpyrrolidone, octylcaprolactam, 1,3-dimethylimidazolinedione, N—formylpiperidine, ,4-diformy1piperazine) and ketones (e. g. acetone, acetophenone, methyl ethyl ketone, methyl butyl ketone).
Preferred diluents used may be any solvent that does not impair the reaction, for example water.
Useful examples are aromatic hydrocarbons such as benzene, toluene, xylene or chlorobenzene; halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane or carbon tetrachloride, hain or cyclic ethers such as diethyl ether, dioxane, tetrahydrofuran or 1,2- dimethoxyethane; esters such as ethyl acetate and butyl acetate; ketones, for example acetone, methyl isobutyl ketone and cyclohexanone; amides such as dimethylformamide and dimethylacetamide, N- pyrrolidone; nitriles such as acetonitrile or propionitrile; and other inert solvents such as 1,3- dimethy1imidazolidinone; the ts may be used alone or in a combination of 2 or more.
In the reactions of the compounds of the structure (W4) with the acetylenes of the structure (W8), it is possible to add bases. Examples include alkaline earth metal or alkali metal compounds (e.g. hydroxides, hydrides, oxides and carbonates of lithium, sodium, potassium, magnesium, calcium and barium), amidine bases or guanidine bases (e.g. 7-methyl-1,5,7-triazabicyclo[4.4.0]decene (MTBD); icyclo[4.3 .0]nonene (DBN), diazabicyclo[2.2.2]octane (DABCO), 1 ,8- diazabicyclo[5.4.0]undecene (DBU), cyclohexyltetrabutylguanidine (CyTBG), cyc1ohexyltetramethylguanidine (CyTMG), N,N,N,N—tetramethyl-1 ,8-naphthalenediamine, pentamethylpiperidine) and amines, especially ry amines (eg. triethylamine, trimethylamine, zylamine, triisopropylamine, tributylamine, lohexylamine, triamylamine, trihexylamine, N,N—dimethylaniline, N,N—dimethyltoluidine, N,N-dimethyl-p-aminopyridine, N—methylpyrrolidine, N- methylpiperidine, N—methylimidazole, N—methylpyrazole, N—methylmorpholine, N— methylhexamethylenediamine, ne, 4-pyrrolidinopyridine, 4-dimethylaminopyridine, quinoline, 0t- picoline, B-picoline, isoquinoline, pyrimidine, acridine, N,N,N',N'—tetramethylenediamine, N,N,N',N'- thylenediamine, quinoxaline, N—propyldiisopropylamine, N—ethyldiisopropylamine, N,N'- dimethylcyclohexylamine, 2,6-lutidine, 2,4-lutidine or triethylenediamine).
A preferred basic reaction auxiliary used may be an c base such as triethylamine, ethyldiisopropylamine, tri-n—butylamine, pyridine and 4-dimethylaminopyridine; in addition, it is possible to use, for example, the following bases: alkali metal hydroxides, for e sodium hydroxide and potassium hydroxide; carbonates such as sodium hydrogencarbonate and potassium carbonate; phosphates such as dipotassium hydrogenphosphate and ium phosphate.
The reaction can be executed within a wide temperature range. Usually, it is conducted within a temperature range from —78°C to 200°C, preferably at temperatures between -10 and 150°C. The \VO 67647 — 131 — PCT/EPZtll4/07379’S reaction can be executed under elevated or else reduced pressure. But it is preferably conducted under standard pressure. The reaction times are between 0.1 and 72 hours, preferably between 1 and 24 hours.
To t the reaction, for example, 1-2 molar equivalents of the compounds of the structure (W8) and 1 molar equivalent up to a slight excess of base per mole of the compound of the structure (W4) are d in a solvent, for example dimethylformamide (DMF).
Stages 3 and 4 for preparation of the compounds of the structure (W5) can be conducted in individual steps or else as a one-pot reaction.
Stages 5, 6 Hydrolysis, amidation 83/ 2 Br Bl§B O _-—> A1/ 6‘ .Az‘AfYo O'Alkyl (W5) (W6) (B7) (1-T22) Inventive compounds of the l structure (I-T22) can be prepared in analogy to e coupling methods known from the literature from the starting materials (W6) and (W9) (W02010051926; WO2010133312). Compounds of the general structure (W6) can be prepared ously to processes known from the literature by ester hydrolysis from compounds of the general structure (W5) (W02010051926; W02010133312). The Al-A4, Bl-Bs, alkyl, Q, R1 and R11 ls are each as defined above.
Process I-T23 id="p-414" id="p-414" id="p-414" id="p-414" id="p-414" id="p-414"
[414] The compounds of the structure (I—T23) can be prepared by the process specified in Reaction Scheme 8.
\VO 2015/067647 ~ 1 b) IQ 2014/G73795 Reaction Scheme 8: A¢A3n2§o H2NOH Aann/KO A! \ A1Y4 IA4 / X-Z o '?‘ Halogenating agent The Al-A4, Bl—B5, alkyl, Q, R1 and R11 radicals are each as defined above. X is, for example, Cl, Br, I.
Stage 1 Oxime Stage 1 of the preparation process for the inventive compounds (I-T23): ,Alk O,Alkyl Yl . / A'I\ A4 A1j/A4/ 0/ t}! X—l X—2 "’0 67647 P'CT/EP2014/073795 Inventive nds of the general structure (X—2) can be prepared in analogy to methods known from the literature from the starting materials of the structure (X-l). The A] -A4 and alkyl ls are each as defined above. Starting compounds of the structure (X-l) are known or can be prepared by known methods. Examples include 3~carbomethoxybenzaldehyde, 3-carbomethoxy—4- chlorobenzaldehyde, 3-carbomethoxybromobenzaldehyde, 3-carbomethoxyfluorobenzaldehyde, 3- ethoxy—4-chlor0fluorobenzaldehyde and the corresponding ethyl esters. They can be prepared, for e, by the methods bed in , p. 19-20; Journal of Organic Chemistry, 76 (2011), p. 1062 — 1071; , p. 137; Journal of the American Chemical Society, 108 (1986), p. 452-461. id="p-418" id="p-418" id="p-418" id="p-418" id="p-418" id="p-418"
[418] The as yet unknown compounds (X—2) can be prepared in analogy to the known ses for preparing oximes from aldehydes (H. Metzger in Houben-Weyl, volume X/4, p. 55 ff., Georg Thieme Verlag Stuttgart 1968). The compounds of the structural formula (X-Z) may be in the form of pure stereoisomers, but also in the form of mixtures of the stereoisomers.
Stage 2 Hydroxamyl chloride id="p-419" id="p-419" id="p-419" id="p-419" id="p-419" id="p-419"
[419] Stage 2 of the preparation process for the inventive compounds (I-T23): Ali/A4 A \ A4 ii" ".V >< 0" OH X-2 X-3 id="p-420" id="p-420" id="p-420" id="p-420" id="p-420" id="p-420"
[420] Inventive compounds of the general structure (X-3) are prepared by reacting the oximes of the structure (X—2) with halogenating agents.
The Al-A4 and alkyl radicals are each as defined above.
Typical compounds of the structure (X-3) are, for example, carbomethoxychloro—N— hydroxybenzimidoyl chloride, omethoxyfluoro—N—hydroxybenzimidoyl de, 3- carbomethoxychlorofluoro-N-hydroxybenzimidoyl chloride, 3-carb0methoxybromo—N— hydroxybenzimidoyl chloride. le nating compounds are known to those skilled in the art, for example chlorine, bromine, iodine, N—chlorosuccinimide, N—bromosuccinimide, N—iodosuccinirnide, 1,3—dichloro-5,5— dimethylhydantoin, l,3-dibromo-5,5-dimethylhydantoin, benzyltrimethylammonium tetrachloroiodate and sodium hypochlorite. Preference is given to using chlorinating reagents. \ - l U) 4; I Useful diluents or solvents for conducting the processes according to the invention in principle include all c solvents which are inert under the specific reaction conditions. Examples include: hydrohalocarbons (cg. hydrochlorocarbons, such as tetraethylene, tetrachloroethane, ropropane, methylene chloride, dichlorobutane, chloroform, carbon tetrachloride, trichloroethane, oroethylene, pentachloroethane, difluorobenzene, l ,2-dichloroethane, chlorobenzene, bromobenzene, dichlorobenzene, chlorotoluene, trichlorobenzene), alcohols (e.g. methanol, ethanol, isopropanol, butanol), ethers (e.g. ethyl propyl ether, methyl tert-butyl ether, n—butyl ether, anisole, phenetole, cyclohexyl methyl ether, dimethyl ether, diethyl ether, dipropyl ether, diisopropyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, dichlorodiethyl ether and polyethers of ethylene oxide and/or propylene oxide), amines (e.g. trimethyl—, triethyl—, tripropyl—, tributylamine, ylmorpholine, pyridine and tetramethylenediamine), nitrohydrocarbons (e.g. nitromethane, nitroethane, nitropropane, nitrobenzene, chloronitrobenzene, 0- nitrotoluene; nitriles such as acetonitrile, nitrile, nitrile, isobutyronitrile, benzonitrile, mchlorobenzonitrile ), tetrahydrothiophene e, dimethyl xide, tetramethylene sulphoxide, dipropyl sulphoxide, benzyl methyl sulphoxide, diisobutyl sulphoxide, dibutyl sulphoxide, diisoamyl sulphoxide, sulphones (e.g. dimethyl, diethyl, dipropyl, dibutyl, diphenyl, dihexyl, methyl ethyl, ethyl propyl, ethyl isobutyl and pentamethylene sulphone), aliphatic, cycloaliphatic or aromatic hydrocarbons (e.g. pentane, hexane, heptane, octane, nonane and technical hydrocarbons), and also what are called "white s" with components having boiling points in the range from, for e, 40°C to 250°C, cymene, petroleum fractions within a boiling range from 70°C to 190°C, cyclohexane, methylcyclohexane, petroleum ether, ligroin, octane, benzene, e, benzene, enzene, nitrobenzene, xylene, esters (e.g. methyl, ethyl, butyl and isobutyl acetate, yl, dibutyl and ethylene carbonate); amides (e.g. hexamethylenephosphoramide, ide, N—methylformamide, N,N- dimethylformamide, N,N-dipropylforrnamide, N,N-dibutylformarnide, ylpyrrolidine, N- methylcaprolactam, 1 ,3 -dimethyl-3 ,4, 5 ,6-tetrahydro—2( 1H)—pyrimidine, yrrolidone, octylcaprolactam, 1,3-dimethyl—2-imidazolinedione, N—formylpiperidine, N,N’-1,4-diformylpiperazine) and ketones (e.g. acetone, acetophenone, methyl ethyl ketone, methyl butyl ).
Preferred diluents used may be any solvent that does not impair the reaction, for example water.
Useful examples are aromatic hydrocarbons such as benzene, toluene, xylene or chlorobenzene, halogenated hydrocarbons such as dichloromethane, chloroform, chloroethane or carbon hloride, open—chain or cyclic ethers such as diethyl ether, dioxane, tetrahydrofuran or 1,2— dimethoxyethane; esters such as ethyl acetate and butyl acetate; s, for example acetone, methyl isobutyl ketone and cyclohexanone; amides such as dimethylformamide and dimethylacetamide, N- methylpyrrolidone; nitriles such as acetonitrile or propionitrile, and other inert solvents such as 1,3- dimethyl—2-imidazolidinone; the solvents may be used alone or in a combination of 2 or more.
The reaction can be executed within a wide temperature range. Usually, it is conducted within a temperature range from —78°C to 200°C, preferably at temperatures between —10 and 150°C. The \VO 2015/067647 — 1 U.) U1 1 on can be executed under elevated or else reduced pressure. But it is preferably conducted under standard pressure. The reaction times are between 0.1 and 72 hours, preferably between 1 and 24 hours.
To perform the reaction, 1 to 3 mol, preferably 1 to 1.5 mol, of nating agent are used per mole of the compound of the structure (X—2) in a solvent, for example ylformamide (DMF).
Stage 3 Ring closure Stage 3 of the preparation process for the inventive compounds (1-T23): O,Alkyl 313// 2, Margo BNB&'81 Ali/44 ——-——> X-3 X-6 Inventive compounds of the general structure (X—4) are prepared by reacting the hydroxamyl chlorides of the structure (X-3) with acetylenes of the structure (X-6).
The Al—A4, Bl-Bs, R11 and alkyl radicals are each as defined above.
Typical compounds of the structure (X-3) are, for example, carbomethoxychlor0—N- hydroxybenzimidoyl de, 3-carbomethoxy—4-fluoro—N—hydroxybenzimidoyl chloride, 3- carbomethoxy—4-chloro—5-fluoro-N-hydr0xybenzimidoyl de, 3-carbomethoxybromo-N— hydroxybenzimidoyl chloride.
Useful diluents or solvents for conducting the processes according to the invention in principle e all organic solvents which are inert under the specific reaction conditions. Examples include: hydrohalocarbons (e.g. hydrochlorocarbons, such as tetraethylene, tetrachloroethane, dichloropropane, methylene chloride, dichlorobutane, chloroform, carbon tetrachloride, trichloroethane, trichloroethylene, pentachloroethane, obenzene, 1 ,2-dichloroethane, chlorobenzene, enzene, dichlorobenzene, chlorotoluene, orobenzene), alcohols (e.g. methanol, ethanol, isopropanol, butanol), ethers (e.g. ethyl propyl ether, methyl tert-butyl ether, n-butyl ether, anisole, phenetole, cyclohexyl methyl ether, dimethyl ether, diethyl ether, dipropyl ether, diisopropyl ether, utyl ether, diisobutyl ether, diisoamyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, dichlorodiethyl ether and polyethers of ethylene oxide and/or propylene oxide), amines (e.g. trimethyl-, triethyl—, tripropyl-, ylamine, N-methylmorpholine, pyridine and tetramethylenediamine), nitrohydrocarbons (e.g. nitromethane, nitroethane, nitropropane, nitrobenzene, chloronitrobenzene, o- oluene; nitriles such as acetonitrile, propionitrile, butyronitrile, isobutyronitrile, benzonitrile, m— chlorobenzonitrile), ydrothiophene dioxide, dimethyl sulphoxide, tetramethylene sulphoxide, - 136 — dipropyl sulphoxide, benzyl methyl sulphoxide, diisobutyl sulphoxide, dibutyl sulphoxide, diisoamyl sulphoxide, sulphones (e.g. dimethyl, diethyl, dipropyl, dibutyl, diphenyl, dihexyl, methyl ethyl, ethyl propyl, ethyl isobutyl and pentamethylene sulphone), aliphatic, cycloaliphatic or aromatic hydrocarbons (e.g. pentane, hexane, heptane, octane, nonane and technical hydrocarbons), and also what are called "White spirits" with ents having boiling points in the range from, for example, 40°C to 250°C, 70°C to cymene, eum fractions within a boiling range from 190°C, cyclohexane, methylcyclohexane, petroleum ether, ligroin, octane, benzene, toluene, benzene, bromobenzene, nitrobenzene, xylene, esters (e.g. methyl, ethyl, butyl and yl acetate, dimethyl, dibutyl and ne carbonate); amides (e.g. hexamethylenephosphoramide, formamide, N-methylformamide, N,N- ylforrnamide, N,N—dipropylformamide, N,N—dibutylformamide, ylpyrrolidine, N- methylcaprolactam, l ethyl—3 ,4,5,6—tetrahydro-2(lH)-pyrimidine, octylpyrrolidone, octylcaprolactam, l,3-dimethyl-2—imidazolinedione, N-formylpiperidine, ,4—diformylpiperazine) and ketones (e.g. acetone, acetophenone, methyl ethyl ketone, methyl butyl ketone).
Preferred diluents used may be any solvent that does not impair the reaction, for example water.
Useful examples are aromatic hydrocarbons such as benzene, toluene, xylene or chlorobenzene; halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane or carbon hloride, open—chain or cyclic ethers such as diethyl ether, dioxane, tetrahydrofuran or 1,2- dimethoxyethane; esters such as ethyl acetate and butyl acetate; s, for example acetone, methyl isobutyl ketone and cyclohexanone; amides such as dimethylformamide and dimethylacetamide, N- methylpyrrolidone; nitriles such as acetonitrile or propionitrile; and other inert solvents such as 1,3- dimethyl—2-imidazolidinone; the solvents may be used alone or in a combination of 2 or more.
In the reactions of the compounds of the structure (X-3) With the acetylenes 0f the structure (X— 6), it is possible to add bases. Examples include alkaline earth metal or alkali metal compounds (e.g. hydroxides, hydrides, oxides and carbonates of lithium, sodium, potassium, magnesium, calcium and ), amidine bases or guanidine bases (e.g. 7-methyl—l,5,7-triazabicyclo[4.4.0]decene (MTBD); diazabicyclo[4.3.0]nonene (DBN), diazabicyclo[2.2.2]octane (DABCO), 1,8- diazabicyclo[5.4.0]undecene (DBU), cyclohexyltetrabutylguanidine (CyTBG), cyclohexyltetramethylguanidine (CyTMG), N—tetramethyl—l ,8-naphthalenediamine, pentamethylpiperidine) and amines, especially ry amines (e.g. triethylamine, trimethylamine, tribenzylamine, triisopropylamine, tributylamine, tricyclohexylamine, triamylamine, trihexylamine, N,N—dimethylaniline, N,N—dimethyltoluidine, N,N—dimethyl-p—aminopyridine, N—methylpyrrolidine, N— methylpiperidine, N—methylimidazole, N—methylpyrazole, N—methylmorpholine, N- methylhexamethylenediamine, pyridine, 4-pyrrolidinopyridine, thylaminopyridine, quinoline, 0t- picoline, B—picoline, noline, pyrimidine, ne, N,N,N',N'—tetramethylenediamine, N,N,N',N'— tetraethylenediamine, quinoxaline, yldiisopropylamine, N—ethyldiisopropylamine, N,N'- dimethylcyclohexylamine, 2,6—lutidine, 2,4-lutidine or triethylenediamine). "’0 2015/067647 - 13 — A preferred basic reaction ary used may be an organic base such as triethylamine, ethyldiisopropylamine, tri-n-butylamine, pyridine and thylaminopyridine; in addition, it is possible to use, for example, the ing bases: alkali metal hydroxides, for e sodium hydroxide and potassium ide; carbonates such as sodium hydrogencarbonate and potassium carbonate; ates such as dipotassium hydrogenphosphate and trisodium phosphate.
The reaction can be executed within a wide temperature range. Usually, it is conducted within a ature range from -78°C to 200°C, preferably at temperatures between -10 and 150°C. The reaction can be executed under elevated or else reduced pressure. But it is preferably conducted under standard pressure. The reaction times are between 0.1 and 72 hours, preferably between 1 and 24 hours. id="p-437" id="p-437" id="p-437" id="p-437" id="p-437" id="p-437"
[437] To conduct the reaction, for example, 1-2 molar equivalents of the compounds of the ure (X-6) and 1 molar equivalent up to a slight excess of base per mole of the compound of the structure (X- 3) are reacted in a solvent, for e dimethylforrnamide (DMF).
Stages 2 and 3 for preparation of the compounds of the structure (X-4) can be conducted in individual steps or else as a one-pot on.
Stages 4, 5 Hydrolysis, amidation The last stages (stages 4 and 5) for preparation of the inventive compounds (l—T23), hydrolysis of the carboxylic ester (X—4) and amidation of the carboxylic acid X-5, can be conducted by the general and amidation of the carboxylic acid. processes described above (Reaction Scheme) for ester ysis Stage 6 Preparation of the acetylenes id="p-440" id="p-440" id="p-440" id="p-440" id="p-440" id="p-440"
[440] Stage 6 Preparation of the starting compounds of the structure (X-6) B3// 2~ B 81 83// 2\|Bl Bl \ /H\ B4QB/LUI + Q -——> 4\ B \R11 Q R11 x7 X-8 X—6 The Bl-Bs, R11 and U radicals are each as defined above. U is, for example, bromine, iodine or triflate. id="p-442" id="p-442" id="p-442" id="p-442" id="p-442" id="p-442"
[442] Inventive compounds of the general structure (X—6) can be prepared in analogy to s known from the literature (Chinchilla, Rafael et al., Chemical Society Reviews (2011), 40(10), p. 5084- 5121, Chinchilla, Rafael et al., Chemical Reviews (Washington, DC, United States) (2007), 107(3), p. 874-922) from the starting materials of the structure (X—7) with catalysis by means of transition metal sts comprising palladium and copper.
\NO 2015/067647 - 138 — Starting compounds of the structure (Ii-37‘) are known 01 can be prepared by idiown s.
Examples include 2-bromo-l,3-dichloro—5-[l,2,2,2—tetrafluoro-l—(trifluoromethyl)ethyl]benzene, 2— bromo—l ,3 —di1nethyl—5 - [l ,2 ,2 ,2 -tetraflu0ro—l -(trifluoromethyl)ethyl]benzene, 2-br01no—l —ethyl-3 -methyl- —[1,2,2,2-tetrafluoro—l-(trifluoromethyl)ethyl]benzene, 2-brom0-1 -chloro—5 -[l ,2,2,2—tetrafluoro—l - (trifluoromethyl)ethyl] -3 -(trifluoromethyl)benzene, 2-bromo-1 -methyl-5 -[1 ,2,2,2-tetrafluor0-l - oromethyl)ethyl] -3 -(trifluoromethyl)benzene, 2-bromochloro-5 — [l ,2,2,2—tetrafluoro-l - (trifluoromethyl)ethyl]-3 -(trifluoromethoxy)benzene, 2-bromo-l -methyl[1 ,2,2,2—tetraflu0ro-1 - (trifluoromethyl)ethyl](trifluoromethoxy)benzene. They can be prepared, for example, by the methods described in EP 1 253 128, pages 8—10. id="p-444" id="p-444" id="p-444" id="p-444" id="p-444" id="p-444"
[444] Starting compounds of the ure (X-8) are known or can be prepared by known s. If R6=H, it is possible in this process to use a protecting group rather than R6. Suitable protecting groups are, for example, trimethylsilyl, ylsilyl and dimethylhydroxymethyl. Further suitable protecting lists in 's tive groups for introduction and detachment are described in the literature [see groups in organic synthesis, 4th edition, P. G. M. Wuts, T. W. Greene, John Wiley & Sons, Inc., Hoboken, New Jersey, 2007, pages 927-933.] Stage 3 alternative: Coupling with amides Alternatively, the inventive nds (I—T23) can be prepared by the general Preparation Process B ion Scheme 9).
Reaction Scheme 9: Q‘N’R1 lea/ 2x‘81 Aann/JPO l\.
A:\IA,1 —-———> "1/ CI X—9 X-6 X-4 The Al-A4, Bl—Bs, Q, R1 and R11 radicals are each as defined above.
Inventive compounds of the general structure (X—4) are prepared by reacting the hydroxamyl chlorides of the structure (X—9) with acetylenes of the ure (X-6). id="p-448" id="p-448" id="p-448" id="p-448" id="p-448" id="p-448"
[448] The preparation of the compounds of the structure (X-6) is described above. The compounds of the structure (X-9) are prepared analogously to the above-described preparation of the compounds of the structure (X-3).
WC) ZOE/067647 — 139 — S Typical compounds of the structure (X—S) are, for example, 4-chloro—3—(cyclopropylcarbamoyl)- N—hydroxybenzimidoyl chloride, 3-(cyclopropylcarbamoyl)—4-fluoro-N-hydroxybenzimidoyl chloride, 4-chloro(cyclopropylcarbamoyl)-5 -fluoro-N-hydroxybenzimidoy1 chloride, 4-bromo (cyclopropylcarbamoyl)-N-hydroxybenzimidoyl chloride.
(I-T24): Compounds of the formula (I-24) can be prepared, for example, analogously to Furukawa, Hirotoshi et a1. Heterocycles, 79 (2009), p. 303-309; US 009, p. 34, Example 111.
(I-T25): Compounds of the formula (I-25) can be prepared, for example, analogously to WO 2004/14366, p. 113.
(I-T26): Compounds of the a (I—26) can be prepared, for example, analogously to Chihiro, shi et al., Journal of Medicinal try, 38 (1995), p. 353-358.
(I—T27): Compounds of the a (I-27) can be prepared, for example, analogously to US 6,545,009, p. 31, Example 74.
The compounds of the ure (I-T28) can be prepared by the process specified in Reaction Scheme 10.
\NO WIS/067647 — 140 - Reaction Scheme 10 B \ ' ' J‘B. // 2 131 1_Actlvat|on 83/ I B3; " B4§B5MO — I; \ HRH—I2 2. Ammonia 4\Bs 0 The Al-A4, Bl-B5, alkyl, Q, R1 and R11 radicals are each as defined above. Starting compounds of the structure (S-l) are known (e..g. US 5,739,083 p. 10, or , p. 117-118) or can be prepared by known methods. The reactions are conducted under the conditions specified in the literature (e.g. ahman S. Mayhoub et a1., Bioorg. Med. Chem. 20 (2012) p. 2427—2434 or WO 2009/023372).
Process I-T29 id="p-456" id="p-456" id="p-456" id="p-456" id="p-456" id="p-456"
[456] The nds of the ure (I-T29) can be prepared by the process specified in Reaction Scheme 11. ‘ — 141 - 2014/073795 Reaction Scheme 3: ,Alkyl ,Alkyl O 3 / Yb I A'\ A H-1 0 0 NH2 8/ 2 B1 R11 1. tion 2- H . ‘R1 The Al—A4, Bl-Bs, alkyl, Q, R1 and R11 radicals are each as defined above. Starting compounds of the structure (H—1) and (H—7) are known (e.g. US 3,725,417 p. 7 or , p. 117—118) or can be prepared by known methods. The reactions are conducted under the conditions specified in the ture (e.g. ahman S. Mayhoub et a1., Bioorg, Med. Chem. 20 (2012) p. 2427-2434 or WO 2009/023372).
Process I-T30 id="p-458" id="p-458" id="p-458" id="p-458" id="p-458" id="p-458"
[458] (I—T30): Compounds of the formula (I-T30) can be prepared, for example, analogously to WO 2011/9484, p. 104; or Gamber, Gabriel G. et a1., Bioorganic and Medicinal Chemistry Letters, 21 (2011), p. 1447-1451.
‘ (I—T31): Compounds of the formula (I—T31) can be ed, for example, analogously to Bishop, Brian C. et al., Synthesis, (2004), 8 p. 43—52; or Heller, Stephen T. et al., Organic Letters, (2006), p. 2675-2678; or Baddar, F.G. et al. Journal rocyclic Chemistry, 15 , p. 385-393.
(I-T32): Compounds of the formula (I-T32) can be prepared, for example, analogously to Joo, Jung Min et al., Journal of Organic Chemistry, 75 (2010), p. 920.
(I-T33): Compounds of the formula ) can be prepared, for example, analogously to Joo, Jung Min et al., Journal of Organic Chemistry, 75 (2010), p. 4911-4920; or , p. 70.
(I-T34): Compounds of the formula (I-T34) can be prepared, for example, analogously to Al— Tel, Taleb et al., Journal of Medicinal Chemistry, 54 (2011), p. 8373-83 85. id="p-463" id="p-463" id="p-463" id="p-463" id="p-463" id="p-463"
[463] (I—T35): Compounds of the formula (I—T35) can be prepared, for example, analogously to Yang, Shu-Wie et al., Bioorganic and Medicinal Chemistry Letters, 21 (2011), p. 182—185; or y, Andrew J. et al, Journal of Medicinal Chemistry, 54 (2011), p. 3524-3548.
The compounds of the structure (I—T45) can be prepared by the s specified in Reaction Scheme 12.
WO 67647 on Scheme 12 /BZ‘B B Bal/ .
BLU B? 2 3: BRBS \ \ CuSO4 BR N (3-1 (R11)n x )U\ 6-2 A1/ A \4 O A2’A3)\E Pd(0) ~Alkyl G-6 B ¢ 2~ 3/8231 :3 f A J8: NB N/MRH)" B4\\B NQARH)" NaOH 5 N 1 . Activatio n Q-N‘R1 BB? 2‘3 The Al-A4, Bl-Bs, alkyl, Q, R1 and R11 radicals are each as defined above. U is a boronic acid, boronic ester or trifluoroboronate. X is bromine, iodine or triflate. Starting compounds of the structure (G-l), (G-5) and (G6) are known or can be prepared by known methods.
The reactions can be conducted by the processes bed in the literature (see, for example Stage G1—>G2 US 2013/0012532, p. 29).
Process I-T46 The compounds of the structure (I-T46) can be prepared by the process specified in Reaction Scheme 13.
Reaction Scheme 13 B \ B 83// 2 $1 2 \ /LN \ Halogenatlon.
BS// . )\N \E31 x 1321\35\ \—) ——-I- BR§BS _ O Pd(0) Az-‘A3 O‘Aikyt 83%B F-5 B4§BAN B I 2\|B1 B? 2~ (R11)n T \ j: NaOH 8N (R ) B5 N 11n F-4 A/ ‘4 O A2:A3)\( F_3 A./ A4 0" 'Az WW 1. Activation O‘Nkyi .N~ R1 B?// 2‘ 8&8)1?N (R1141 1-T46 A1/ 64 o Azan .N~R1 The Al-A4, Bl-Bs, alkyl, Q, R1 and R11 radicals are each as defined above. U is a boronic acid, boronic ester or roboronate. X is bromine, iodine or triflate. Starting compounds of the structure (F—l) and (F-S) are known (e.g. F—l: p, David G. et a1., c Letters, 9 (2007), p. 1761-1764) or can be prepared by known methods.
The reactions can be conducted by the processes described in the literature, for example US 2009/209476, p. 18-19.
Process I—T47 id="p-470" id="p-470" id="p-470" id="p-470" id="p-470" id="p-470"
[470] The compounds of the structure (I—T47) can be prepared by the process specified in Reaction Scheme 14.
V170 2015/067647 - 145 — PCT/EP’2014/073795 Rea cticn Scheme 11 1. Activation ¢A3 \O ATAIW/K 2. AlkyIOH (mph—QBE-1E'2R01R8 Halogenation 8% 2‘B BFB u O.Alkyl O‘Alkyl M NaOH B 1.Activation B// 24 B 2. B B] I1 Q-N‘R‘l 53% 4% (R 2181 Bs 11 )n B4§Bs/I\EW(R11)n| A/ A ‘4 0 1-T47 E-5 A)\A4 o AgiA 1_ H 3 OH Azs'Aa The Al-A4, Bl-Bs, alkyl, Q, R1 and R11 radicals are each as defined above. U is bromine, iodine or triflate when M is a boronic acid, c ester or trifluoroboronate. U is a boronic acid, c ester or trifluoroboronate when M is e, iodine or triflate. ng compounds of the ure (E—l) and (E-6) are known (e.g. Liu, Kun et al., Journal of Medicinal Chemistry, 51 (2008), p. 7843—7854; or Cornet, Stephanie M. et al., Transactions, (2003), p. 4395—4405), or can be prepared by known methods.
The reactions can be conducted by the processes described in the literature, for example US 2009/209476, p. 18-19.
Process for preparing thioamidcs The compounds of the structure (Ii) can be ed by the process specified in Reaction Scheme 15 from compounds of the structure (Ih) through reaction with sulphur-transferring reagents.
W'O 2015/067647 — 146 — Reaction Scheme 15: 8‘ B\ 83’ 38L 83’ 38L BRBS T Thlonatmg reagent BRBS T _—..—> A )\A Al/ \I1 O A1l/ \4 S A2§A3 A2§A3 N\ N\ R1/ Q RV Q (1h) (2) (Ii) The A1-A4, Bl—Bs, alkyl, Q, T and R1 radicals are each as defined above. The thionating reagent (2) used may, for example, be P4810 0r Lawesson's reagent (2,4—bis(4-methoxyphenyl)—l,3,2,4- dithiadiphosphetane 2,4-disulphide).
The preparation of the compounds (Ih) is described above.
The thionating reagents are commercially available or can be prepared by processes known to those skilled in the art or in analogy to these processes. id="p-477" id="p-477" id="p-477" id="p-477" id="p-477" id="p-477"
[477] The reaction is conducted in analogy to methods known from the literature for ting carbonamides (e.g. W02012056372, p. 77; W02003066050, p. 31).
Process for preparing (Ik) The inventive compounds (Ik) can be prepared by the process specified in Reaction Scheme 16 from the compounds (Ij) through reaction with sulphur compounds of the ure (Y-3).
Reaction Scheme 16 32. 13¢ " B? ) [8‘ B? Iii [LSAT lY 4V T X 2—K, O + RM/S R14/S >_/ \V0 ZOE/(167647 — 147 — PCT/liPZUM/(JBWS The reaction is conducted in analogy to methods known from the ture for imroduction oi alkylthio radicals into aromatic systems [e.g. Organometallics 1989, 8(5), 1303-1308; W01998056761, Example 63, p. 97].
Process for preparing glka] and glkb] The inventive compounds (Ika) and (Ikb) can be prepared by the process specified in Reaction Scheme 17 from the compounds of the structure (Ik) through reaction with oxidizing reagents.
Reaction Scheme 17: tafsz‘le, BKB’B, 53/3"'1 avg as ' ‘fl. T _ 85L A O RM’S A.)—A o :0 A R""S‘o A/\ $4 -‘>—< R"’S\‘O AK Ho A~,--AJ ‘N‘Q AEAJ .N"0 A?" aN'Q R R R (Ika) (Ik) (Ikb) The A1 to A4, B1 to B4, alkyl, Q, R, n and R11 radicals are each as defined above. R14 is optionally tuted C1—C6-a1ky1.
The preparation of the compounds of the structure (Ik) is described above.
The oxidizing agents used may be the reagents known to those skilled in the art from the literature for preparation of sulphoxides and nes. They are commercially available or can be prepared by processes known to those skilled in the art or in analogy to these processes. Examples include: hydrogen peroxide, peroxyacetic acid, 3-chloroperbenzoic acid and trifluoroperoxyacetic acid.
The on is conducted in analogy to s known from the literature for preparation of sulphoxides and nes [sulphoxide derivatives: W02006/097766; WO2005/019151; sulphone derivatives: W02008/125214; /121087]. s for re nrin N-al lcomlounds The compounds of the structure (I) can be prepared by the process specified in Reaction Scheme 18 from compounds of the structure (Im) through reaction with alkylating agents.
\VO 2015/067647 - 148 — PCT/EPZOl4/87379S Reaction Scheme 18: ,.,B. - B , B;/ a )8; B3// 2 g; B‘\ T Base B\4§B T (1111) (I) The Al—A4, B1-B5, alkyl and Q radicals are each as defined above. U is, for example, bromine, iodine or triflate. R1 is in each case primary or secondary, optionally substituted C1-C6-alkyl, C3-C6- alkenyl, C3—C6-alkynyl, C4-C7-cycloalkyl, C1—C6—alkylcarbonyl, C1—C6-alkoxycarbonyl, aryl-(Cl-C3)— alkyl, heteroaryl-(Cl-C3)—alkyl. W is oxygen.
Compounds of the structure U—R1 are commercially available or known from the literature, or can be prepared in analogy to methods known from the literature. Examples include: methyl chloride, methyl bromide, methyl iodide, dimethyl sulphate, methyl triflate, ethyl bromide, ethyl iodide, diethyl sulphate and ethyl triflate.
The bases used for the on are commercially available. Examples include alkaline earth metal and alkali metal compounds (eg. ides, hydrides, oxides and carbonates of lithium, sodium, potassium, magnesium, m and barium), for example sodium hydride, sodium hydroxide and ium hydroxide; carbonates such as sodium hydrogencarbonate and potassium carbonate.
The reaction is conducted in analogy to methods known from the literature for N—alkylation of secondary amides (e.g. G.L. Gisele, A. Liittringhaus, Synthesis (1971) p. 266, for an overview see: B.C.
Challis, J.A. s in: The Chemistry of Functional Groups, The try of Amides, S. Patai, J.
Zabicky, editors, cience Publishers, London, 1970, p. 734 ff).
Pre aration of the 4-he tafluoroiso r0 vlmetll ltrifluorometh laniline startin material The 4-heptafluor0isopropyl—Z-methyl—6-trifluoromethylaniline ng al of the structure (D-la) has not been described to date in the literature. The preparation can be conducted by 2 different processes.
W0 2015/00/64? — 1‘49 » l’C’I/EP2014/07379’5 Process for ing thioamides The compounds of the structure (Ii) can be prepared by the process bed in Reaction Scheme 15 from compounds of the structure (Ih) by reaction with sulphur-transferring reagents.
Reaction Scheme 15 B//2B 1 B1 3\ kl, 3\ % a Ing reagent. t B4§Bs )\ B4§B5 )\ A / A / 1‘ \4 O 1. \4 A2§A3 A2§A3 N \Q J" \Q R1 R1 (111) (2) (1i) The Al-A4, Bl-Bs, alkyl, Q, T, and R1 ls are each as defined above. Thionating reagents (2) used may, for example, be P4810 or Lawesson’s t (2,4-bis(4-methoxyphenyl)-l,3,2,4— dithiadiphosphetane 2,4-disulphide).
The preparation of the compounds (Ih) is described above.
The thionating reagents are commercially available or can be prepared by processes known to those skilled in the art or in analogy to these processes. id="p-496" id="p-496" id="p-496" id="p-496" id="p-496" id="p-496"
[496] The reaction is conducted in analogy to methods known from literature for thionation of carbonamides (ag. W02012056372, p. 77; WO2003066050, p. 31).
Process for preparing (Ik) The inventive compounds (Ik) can be ed by the process specified in Reaction Scheme 16 from the compounds (Ij) by reaction with sulphur compounds of the structure (Y-3).
\VO 2015/067647 — 150 — PC’F/EP2014/073795 Reaction Scheme 16 B. /BE~ Bf A131 B?/ IB1 I ‘ B,\ Y T B‘fi/kr é ’ S A 4 o X >— . , A1/ 63—?) + R R" A1/_ ‘) AEAS A2=A3 N—Q 1N_Q R11 R (U) (Y-3) (1k) id="p-498" id="p-498" id="p-498" id="p-498" id="p-498" id="p-498"
[498] The A1 to A4, B1 to B4, alkyl, Q, R1, n and R11 radicals are each as defined above. X is a suitable leaving group, for example fluorine, chlorine, e or iodine. R14 is optionally substituted C1-C6- alkyl. Y is hydrogen or an alkali metal, for example sodium or lithium.
The reaction is conducted in y to methods known from the literature for introduction of alkylthio radicals into ics [e.g. Organometallics 1989, 8(5), 1303—1308; WOl998056761, Example 63,p. 97].
Process 1: 4-Heptafluorois0propyl-2—methyltrifluoromethylaniline of the structure (K—l) can be ed proceeding from 2—methyltrifluoromethylaniline by the process specified in Reaction Scheme 1, by reaction with heptafluoroisopropyl iodide in the presence of hydrogen peroxide.
Reaction Scheme 4 F F \ NH2 I l + F + HO-OH ——> 2-methyl~6-trifluoromethylaniline is known from literature (John P. Chupp, Terry M. Balthazor, Michael J. Miller, and Mark J. Pozzo, J. Org. Chem. 49 (1984),47l 1-4716 or Thomas E. Nickson J. Org.
Chem. 51 (1986) 3903-3904), and heptafluoroisopropyl iodide is commercially available.
The on is ted in analogy to known processes for trifluoromethylation of aromatics (Tatsuhito Kino, Yu Nagase, Yuhki Ohtsuka, Kyoko Yamamoto, Daisuke Uraguchi,Kenji Tokuhisa and Tetsu Yamakawa, l of Fluorine Chemistry 131 (2010) 98—105). — 151 - PCT/EPZGM/(LBWS Process 2 In addition, 4—heptafluoroisopropyl—2-methyl—6-t1‘ifluoromethylaniline of the structure (K—l) can be prepared proceeding from 4-heptafluoroisopropylmethylaniline by the process specified in Scheme 2, by reaction with sodium trifluoromethylsulphinate in the presence of oxidizing agents and tion metal catalysts.
Reaction Scheme 5 H2 H2 F F F + F +X + catalyst + oxidizing agent -—> F F F F F F D—la X is Br, I, NaSOZ' (sodium romethylsulphinate), KSOZ' (potassium trifluoromethylsulphinate).
Particular preference is given to sodium trifluoromethylsulphinate. 4-Heptafluoroisopropylmethylani1ine is known (US2004/92762).
Suitable catalysts are transition metals such as iron(II) te, iron(III) nitrate, copper(II) triflate or ferrocene. Particular ence is given to iron(II) sulphate.
Suitable oxidizing agents are, in particular, peroxides such as hydrogen peroxide, tert-butyl hydroperoxide or sodium peroxodisulphate, potassium peroxodisulphate, sodium peroxomonosulphate or potassium peroxomonosulphate. Particular ence is given to tert—butyl hydroperoxide.
In the performance of the reaction, suitable solvents may be used.
Useful diluents or solvents for performance of the processes according to the invention in principle include all organic solvents that are inert under the c reaction conditions. es include: nitriles such as acetonitrile, propionitrile, butyronitrile, isobutyronitrile; water, tetrahydrothiophene e, yl sulphoxide, tetramethylene xide, dipropyl xide, diisobutyl sulphoxide, dibutyl sulphoxide, diisoamyl sulphoxide, sulphones (e.g. dimethyl, diethyl, dipropyl, dibutyl, dihexyl, methyl ethyl, ethyl propyl, ethyl isobutyl and nethylene sulphone); aliphatic, cycloaliphatic (e.g. pentane, hexane, heptane, octane, nonane and technical hydrocarbons), and also What are called "white spirits" having components having g points in the range from, for example, 40°C to 250°C, petroleum fractions Within a boiling range from 70°C to 190°C, cyclohexane, methylcyclohexane, petroleum ether, ligroin, octane.
Preferred diluents used may be any solvent that does not impair the reaction, for example water; nitriles such as acetonitrile, propionitrile, butyronitrile, isobutyronitrile. The ts can be used alone or in a combination of 2 or more.
‘NO 2015/067647 >1 U1 lo I Bases may be used in the reactions. Examples include alkaline earth metal or alkali metal compounds (6. g. hydroxide, liydrides, oxides and carbonates of lithium, sodium, potassium, magnesium, calcium and barium).
A preferred basic reaction ary used may be sodium hydrogencarbonate; in addition, it is possible, for example, to use the ing bases: alkali metal hydroxides, for example sodium hydroxide and ium hydroxide; carbonates such as sodium hydrogencarbonate and potassium ate; phosphates such as sodium dihydrogenphosphate, dipotassium hydrogenphosphate and trisodium phosphate.
The reaction can be conducted within a wide temperature range. It is usually conducted within a temperature range from -78 to 200°C, ably at temperatures n -10 and 150°C. The reaction can be executed under elevated or else reduced pressure. But it is preferably ted under standard between 1 and 24 hours. pressure. The reaction times are between 0.1 and 72 hours, preferably To conduct the reaction, 1 to 10 mol, preferably 1 to 4 mol, of trifluoromethylating agent; 1 to mol, preferably 1 to 8 mol, of oxidizing agent and 0.01 to 1 mol, preferably 0.05 to 0.4 mol, of catalyst per mole of 4-heptafluoroisopropyl—Z-methyltrifluoromethylaniline are used in a solvent or solvent mixture, for example in a mixture of acetonitrile and water.
\VO 2015/0676447 ~ 1 U] U.) I Process I-T46 extended The compounds of the structure (I—T46) can be prepared by the process specified in the Reaction Scheme.
Reaction Scheme 6 A1 \4 0 A2UABM Pd(0) 0 ‘Alk yI BKBZB1 ' 4\B5 R11)" 3| k NaOH B4\\B5 R11) A \ F'4 AllA/ZAa‘4O F'3 A/ A3 0 A2A3)\§ 1. activation ‘Alkyl QN‘R1 B8:3:82131 \Bs LE;11 1-T46 A A4 1 \AzAaW N‘R1 The Al-A4, Bl-Bs, alkyl, Q, R1 and R11 radicals are each as defined above. U is a boronic acid, boronjc ester or trifluoroboronate. X is bromine, iodine or triflate. ng compounds of the structure (F-l) and (F-S) are known (e.g. F-l: Hulcoop, David G. et a1., Organic Letters, 9 , p. 1761-1764, Supporting information pages 1 ff), or can be prepared by known methods (for example from D—l). id="p-516" id="p-516" id="p-516" id="p-516" id="p-516" id="p-516"
[516] The reactions can be conducted by the processes described in the literature, e.g. /209476, p. 18-19. _S~tz; go 1 pyrrolc ring closure Stage 1 for the preparation process for the inventive Compounds (I—T46): W0 2015/067647 — 154 — PC'E/E92014/07379-5 | / o o o B NH B\§ )\N \ BRB 4 2 35 — D-l F-lb F-l Inventive compounds of the general structure (F-l) can be prepared in analogy to methods known from the literature from the starting materials of the structure (D-1) and (F-lb). The Bl-BS radicals are each as defined above. The compounds of the structures (D-l) are known from the literature (e.g. US2002/198399, W02009/30457, page 28) or can be ed by methods known from the literature. The compound (Fl—b) is commercially available. Typical representatives of the compounds of the structure (D—l) include 2-amino-l ,3 -dichloro-5 -[1 —tetrafluoro-1 — (trifluoromethyl)ethyl]benzene, 2-amino—l ,3 -dimethyl-5 -[l ,2,2,2-tetrafluoro-1 uoromethyl)- ethyl]benzene, 2-aminoethyl—3—methyl-5—[1,2,2,2-tetrafluoro-l-(trifluoromethyl)ethyl]benzene, 2- l -chlor0-5 -[1,2,2,2—tetrafluoro-l -(trifluoromethyl)ethyl]-3 —(trifluoromethyl)benzene, 2-amino—1 — methyl—S-[l,2,2,2—tetrafluoro-l-(trifluoromethyl)ethyl](trifluoromethyl)benzene, 2- amino chloro- -[1 ,2,2,2-tetrafluoro-1 -(trifluoromethyl)ethyl](trifluoromethoxy)benzene, o-1 —methyl ,2-tetrafluoro(trifluoromethyl)ethyl](trifluoromethoxy)benzene. The reaction is conducted under the conditions known for analogous compounds in the literature (e.g. Hulcoop, David G. et al., Organic Letters, 9 (2007), p. 1761-1764, Supporting information pages 1 ff.) Stage 2 halogenatiou Stage 1 for the preparation process for the inventive compounds (I-T46): B \//B?-13\1 834% )WQ\1 nation ___> §4§BSHDA F—l F—2 Inventive compounds of the general structure (F-2) can be ed in analogy to methods known from literature from the starting materials of the structure (F-l) by halogenation. The Bl-B5 radicals are each as defined above. The compounds of the structures (F-l) are known from the ture (e.g. F-l: Hulcoop, David G. et al., Organic Letters, 9 (2007), p. 1761—1764, Supporting ation page 1 ff.) or can be prepared by the method described above. Typical representatives of the compounds of the structure (F-l) include 1-[2,6—dichloro[l,2,2,2—tetrafluoro—l— (trifluoromethyl)ethyl]phenyl]pyrrole, l dimethyl [1 ,2,2,2-tetrafluoro (trifluoromethyl)ethyl]phenyl]pyrrole, 1- [2-ethyl—6~methyl[l ,2,2,2—tetrafluoro—l - (trifluoromethyl)ethyl]phenyl]pyrrole, 1 —[2—chloro[ l ,2,2,2—tetrafluoro-l -(trifluoromethyl)ethyl] VVO 2015/067647 (trifluoromethyl)phenyl]pyirole, l —[2 -methyl[l ,2,2,2-tetrafluoro—l -(t1‘ifluoromethyl)ethyl] (trifluoromethyl)phenyl]pyrrole, l—[l —chloro-5 -[l ,2,2,2—tetrafluoro—l —(trifluoromethyl)ethyl] -6— (trifluoromethoxy)phenyl]pyn‘ole, l - [1 l-5 —[ l ,2 ,2,2-tetrafluoro-l luoromethyl)ethyl] (trifluoromethoxy)phenyl]pyrrole. id="p-519" id="p-519" id="p-519" id="p-519" id="p-519" id="p-519"
[519] Suitable halogenating compounds are known to those skilled in the art, for example bromine, iodine, N—bromosuccinimide, N—iodosuccinimide, l,3-dibromo-5,5-dimethylhydantoin and benzyltrimethylammonium tetrachloroiodate. Preference is given to using bromine, iodine and iodosuccinimide. The reaction follows the conditions known from ture (e.g. Tatsuta; Itoh Bulletin of the Chemical Society of Japan, 67 (1994) 1449-1455).
Sta 6 3 boronic acid cou )lin Stage 3 of the preparation process for the inventive compounds (I-T46): 82 u | A"'81 B3\// )\ N (RM‘ A1\/ A4 Ba§85 N 0 \ BR, 3/ __9 3 O‘Alkyl A1/ 64 o AziAH O‘Alkyl F—2 F—S F-3 The A1 to A4, B1 to B5, alkyl, 11 and R11 radicals are each as defined above. U is, for e, a boronic acid, boronic ester or trifluoroboronate, X is bromine, iodine or triflate.
Inventive nds of the l structure (F—3) can be prepared by processes known from the literature by means of palladium-catalysed reactions from the co—reactants of the general structure (F—2) and (F-S) (e.g. or ). The compounds of the general structure (F-S) are either commercially available or can be prepared by processes known to those skilled in the art.
Stages 4, 5 hydrolysis. amidation H B B /B N\ 2~ B? 2'81 33/ 2'31~ ‘ R1 Q Bl la1 I 1 I B \ / B4\\B ' N (R11)n N 0211)" \N n —> 4\B5 a \ B-7 F-3 \ / A A/ 4 A‘/ I?" A O F'4 ‘4 O A'A. 9Y0 Ay-‘AM A2:A,)\( 1-T46 TAR . N 3 5 NR1 O~ OH , Alkyl Q Inventive compounds of the general structure (I—T46) can be prepared in analogy to peptide coupling methods known from literature from the starting als (F-4) and (B—7) (eg. W0 2010/051926 or WO 33312). Compounds of the general structure (F-4) can be prepared in "’0‘ 2015/067647 — 156 — analogy to processes known from the literature by ester ysis from compounds of the general stlucture (F-3) (e.g. or WO 33312). The Al to A4, B1 to B5, alkyl, Q, R1 and R11 radicals are each as defined above.
In a more preferred embodiment Q in a compound of the formula (I) or (Ia") or (IT-2) or (I-T3) or (I-T4) or (I-T22) or (I-T23) or (I-T46) is C1-C4-alkyl, 2—ox0(2,2,2~trifluoroethylamino)ethyl, fluorine- or l-cyanopropyl- or pyridine-substituted C1-C4—alkyl such as 2,2,2-trifluoroethyl, 2,2- difluoroethyl, trifluoropropyl, n—2-y1methyl or (1-cyanocyclopropyl)methyl; C3-C4— cycloalkyl such as cyclopropyl or cyclobutyl; optionally substituted C3—C4-cycloalkyl such as optionally fluorine-substituted C1-C4-alkyl—substituted ropyl (e.g. 1-trifluoromethyl-cyclopropyl, 1-tert— butylcyclopropyl), 1-thiocarbamoylcyclopropyl, 1-carbamoylcyclopropyl, l-cyanocyclopropyl, trans—2- fluorocyclopropyl, cisfluorocyclopropyl; C4-C6-heterocycloalkyl such as oxetan—3-yl, thietan—3-yl, 1- oxidothietan—B-yl, or 1,1-dioxidothietan—3-yl; or each case optionally C1—C4—alkyl-substituted benzyl; pyrazole (such as N—methylpyrazol—3-yl), pyridine; sulphonyl; or 2-oxo-2—(2,2,2- trifluoroethylamino)ethyl.
In a particularly preferred embodiment Q in a compound of the formula (I) or Ga") or (IT-2) or (I—T3) or (I-T4) or (I-T22) or ) or (I-T46) is fluorine-substituted C1-C3-alkyl such as 2,2,2- trifluoroethyl or 3,3,3-trifluoropropyl; cyclopropyl; optionally cyano~, C1-C4-alky1-substituted cyclopropyl such as l—cyanocyclopropyl or l-trifluoromethylcyclopropyl; thietan—3-y1; or 2~oxo—2- 2O (2,2,2-trifluoroethyl)aminoethyl.
Formula (I) A further preferred embodiment relates to compounds of the formula (I) in which T is T2, T3, T4, T22, T23 or T46 and all the other parameters are as defined in paragraph [9].
A further preferred ment relates to compounds of the formula (I) in Which T is T2, T3, T4, T22, T23 or T46 and all the other parameters are as defined in paragraph [9].
A further preferred embodiment s to compounds of the formula (I) in which T is T2 or T4 and all the other parameters are as defined in paragraph [9].
A r preferred embodiment relates to compounds of the formula (I) in which T is T3 or T46 and all the other parameters are as defined in paragraph [9]. id="p-529" id="p-529" id="p-529" id="p-529" id="p-529" id="p-529"
[529] A further preferred embodiment relates to compounds of the formula (I) in which T is T22 or T23 and all the other parameters are as defined in paragraph [9].
A further preferred embodiment s to compounds of the formula (I) in which T is T2, T3, T4, T22, T23 or T46, B3 is C-R8 and R8 is a (C1-C6)-alkyl, )-alkoxy or alkylsulphanyl, each of "’0 2015/067647 which is substituted, where the substituents are ed from halogen and yl, where at least one tuent is halogen and all the other parameters are as defined in paragraph [9].
A r preferred embodiment relates to compounds of the formula (I) in which T is T2, T3, T4, T22, T23 or T46, B3 is C—R8 and R8 is a (Cl-C6)-alkyl, (Cl-C6)—alkoxy or alkylsulphanyl, each of which is substituted, where the substituents are selected from halogen and hydroxyl, where at least one substituent is halogen and all the other parameters are as defined in paragraph [9].
A further preferred embodiment relates to compounds of the formula (I) in which T is T2 or T4, B3 is C-R8 and R8 is a (Cl-C6)-alky1, (Cl—C6)-alkoxy or ulphanyl, each of which is tuted, where the tuents are selected from halogen and hydroxyl, where at least one substituent is halogen and all the other parameters are as defined in paragraph [9].
A further preferred embodiment relates to compounds of the formula (I) in which T is T3 or T46, B3 is C-R8 and R8 is a (Cl-C6)-alkyl, (C1-C6)-alkoxy or alkylsulphanyl, each of which is substituted, where the substituents are selected from halogen and hydroxyl, where at least one substituent is halogen and all the other parameters are as defined in paragraph [9]. id="p-534" id="p-534" id="p-534" id="p-534" id="p-534" id="p-534"
[534] A further preferred embodiment relates to compounds of the formula (I) in which T is T22 or T23, B3 is C—R8 and R8 is a (C1-C6)—alkyl, (C1-C6)-alkoxy or alkylsulphanyl, each of which is substituted, where the substituents are selected from halogen and hydroxyl, where at least one tuent is halogen and all the other parameters are as defined in paragraph [9]. In this context, a particularly preferred embodiment relates to compounds in which R8 is perfluorinated (C1—C6)—alkyl, (Cl-C6)-alkoxy or alkylsulphanyl, most preferably perfluorinated (Cl -C4)—alkyl, (Cl -C4)-alkoxy.
A further preferred embodiment relates to compounds of the formula (I) in which T is T2, T3, T4, T22, T23 or T46, B3 is C-R8 and R8 is a (C1-C6)-alkyl, (C1-C6)—alkoxy or ulphanyl, each of which is substituted, where the substituents are selected from halogen and hydroxyl, where at least one substituent is halogen, more preferably in which R8 is perfluorinated (Cl-C6)-alkyl, (Cl-C6)~alkoxy or alkylsulphanyl, most preferably rinated (C1-C4)—alkyl, (C1—C4)—alkoxy, in which B1, B2, B4 and B5 are, respectively, CR6, CR7, CR9 and CR10 in which R6, R7, R9 and R10 are each independently H, halogen, cyano, nitro, or alkyl, C3—C4—cycloalkyl, C1-C4—alkoxy, xyiminoalkyl, C1-C4- alkylsulphanyl, C1-C4-alkylsulphinyl, C1-C4—alkylsulphonyl, 4-alkylamino, N,N—di-C1-C4- alkylamino, each of which is substituted by at least one substituent selected from halogen and hydroxyl, where at least one substituent is a halogen, and all the other parameters are as defined in paragraph [9].
In a further preferred embodiment, R6 and R10 are each n (such as Cl, Br or F), each C1-C3-alkyl, or each halogen-substituted C1—C3—alky1, for example perfluorinated alkyl (perfluoromethyl, perfluoroethyl or ropropyl).
A further preferred embodiment relates to compounds of the formula (I) in which T is T2, T3, T4, T22, T23 or T46, B3 is C—R8 and R8 is a (Cl-C6)—alky1, (Cl-C6)—alkoxy or alkylsulphanyl, each of PCT/EPZUI4/O7379S which is substituted, where the substituents are selected from halogen and hydroxyl, where at least one substituent is halogen, more preferably in which R8 is perfluorinated (Cl-C6)-alkyl, (Cl—C6)-alkoxy or alkylsulphanyl, most preferably perfluorinated (Cl-C4)-alkyl, (Cl—C4)-alkoxy, in which B1, B2 and B4 are, respectively, CR6, CR7 and CR9 and B5 is N, in which R6, R7 and R9 are each independently H, halogen, cyano, nitro, or C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-alkoxy, N—alkoxyiminoalkyl, C1-C4- alkylsulphanyl, C1-C4—alkylsulphinyl, C1-C4—alkylsulphonyl, N—Cl-C4—alkylamino, N,N—di-C1-C4- alkylamino, each of which is substituted by at least one substituent ed from halogen and hydroxyl, where at least one substituent is a n, and all the other parameters are as defined in paragraph [9].
A further preferred embodiment relates to compounds of the formula (I) in which T is T2, T3, T4, T22, T23 or T46, B3 is C-R8 and R8 is a (C1-C6)—alkyl, (C1-C6)-alkoxy or alkylsulphanyl, each of which is substituted, where the substituents are selected from halogen and hydroxyl, where at least one substituent is halogen, more preferably in which R8 is perfluorinated (Cl-C6)-alkyl, (Cl—C6)—alkoxy 0r alkylsulphanyl, most preferably perfluorinated (Cl-C4)-alkyl, (Cl-C4)-alkoxy, in which B1, B2, B4 and B5 are, respectively, CR6, CR7, CR9 and CR10 in which R6, R7, R9 and R10 are each independently H, halogen, cyano, nitro, or C1-C4-alkyl, C3-C4-cycloalkyl, alkoxy, N—alkoxyiminoalkyl, C1-C4— alkylsulphanyl, Cl-C4-alkylsulphinyl, C1-C4-alkylsulphonyl, N—Cl-C4-alkylamino, -Cl-C4- alkylamino, each of which is tuted by at least one substituent selected from halogen and hydroxyl, where at least one tuent is a halogen, each R11 is independently H, amino (NT-12) or cyano, preferably H, W is O, R1 is H, , ethyl, yl, isopropyl, n—butyl, isobutyl, s-butyl, t-butyl, preferably H or methyl, and all the other parameters are as d in paragraph [9]. In a further preferred embodiment, R6 and R10 are each n (such as Cl, Br or F), each C1—C3-alkyl, or each halogen—substituted C1-C3-alkyl, for example perfluorinated C1-C3-alky1 (perfluoromethyl, perfluoroethyl or perfluoropropyl).
A further preferred embodiment relates to nds of the a (I) in which T is T2, T3, T4, T22, T23 or T46, B3 is C-R8 and R8 is a (Cl—C6)-alkyl, (Cl-C6)—alkoxy or alkylsulphanyl, each of which is substituted, where the substituents are selected from halogen and hydroxyl, where at least one substituent is halogen, more preferably in which R8 is rinated (Cl-C6)-alkyl, (Cl-C6)-alkoxy or alkylsulphanyl, most preferably perfluorinated (Cl-C4)-alkyl, (C1—C4)—alkoxy, in which B1, B2 and B4 are, respectively, CR6, CR7 and CR9 and B5 is N, in which R6, R7 and R9 are each independently H, halogen, cyano, nitro, or C1-C4—alkyl, cycloalkyl, C1—C4—alkoxy, N—alkoxyiminoalkyl, C1-C4- alkylsulphanyl, C1-C4-alkylsulphinyl, C1—C4-alkylsulphonyl, N—Cl-C4-alkylamino, N,N—di-Cl-C4- alkylamino, each of which is substituted by at least one substituent selected from halogen and hydroxyl, where at least one substituent is a n, each R11 is independently H, amino (NT-12) or cyano, preferably H, W is O, R1 is H, methyl, ethyl, n—propyl, isopropyl, n—butyl, isobutyl, s-butyl, t-butyl, preferably H or , and all the other parameters are as defined in paragraph [9].
‘NO 2015/067647 — 159 — A fuither preferred embodiment relates to compounds of the formula (I) in which T is T2, T3, T4, T22, T23 or T46, B3 is C-R8 and R8 is a (Cl—C6)-alkyl, (Cl—C6)—alkoxy or alkylsulphanyl, each of which is substituted, where the substituents are selected from halogen and hydroxyl, where at least one substituent is halogen, more preferably in which R8 is perfluorinated )-alkyl, (C1-C6)-alkoxy 0r alkylsulphanyl, most preferably perfluorinated (C1-C4)-alkyl, (C1-C4)-alkoxy, in which B1, B2, B4 and B5 R10 are each independently H, are, respectively, CR6, CR7, CR9 and CR10 in which R6, R7, R9 and halogen, cyano, nitro, or C1-C4—alkyl, C3-C4-cycloalkyl, C1-C4-alkoxy, N—alkoxyiminoalkyl, Cl-C4- alkylsulphanyl, alkylsulphinyl, C1-C4-alkylsulphonyl, N—Cl-C4-alkylamino, N,N-di-C1—C4- alkylamino, each of which is substituted by at least one substituent selected from halogen and hydroxyl, where at least one substituent is a halogen, each R11 is independently H, amino (NHz) or cyano, preferably H, W is O, R1 is H, methyl, ethyl, n—propyl, isopropyl, n—butyl, isobutyl, s-butyl, t—butyl, preferably H or methyl, Q is C1-C4-alkyl, 2—oxo(2,2,2~trifluoroethylamino)ethyl, e— or 1— cyanopropyl- or pyridine-substituted C1-C4-alkyl such as trifluoroethyl, 2,2—difluoroethyl, 3,3,3- ropropyl, pyridin-Z-ylmethyl or (1-cyanocyclopropyl)methyl; C3—C4—cycloalkyl such as ropyl or cyclobutyl; optionally substituted C3-C4—cycloalkyl such as optionally fluorine- substituted C1-C4-alkyl-substituted cyclopropyl (e.g. 1-triflu0romethylcyclopropyl, l—tert- butylcyclopropyl), l-thi0carbamoylcyclopropyl, l-carbamoylcyclopropyl, 1-cyanocyclopropyl, trans fluorocyclopropyl, cis—2-fluorocyclopropyl; C4-C6-heterocycloalkyl such as oxetanyl, thietan-3—yl, 1- oxidothietan—3-yl, or 1,1-dioxidothietanyl; or in each case optionally Cl-C4-alkyl-substituted benzyl; pyrazole (such as N—methylpyrazolyl), pyridine; sulphonyl; or 2-0xo(2,2,2- roethylamino)ethyl, preferably fluorine-substituted C1-C3-alkyl such as 2,2,2-trifluoroethyl or 3,3,3-trifluoropropyl; cyclopropyl; optionally substituted ropyl such as 1—cyanocyclopropyl or 1- trifluoromethylcyclopropyl, thietanyl; or 2-oxo(2,2,2-trifluoroethyl)aminoethyl, and all the other ters are as defined in aph [9]. In a further red embodiment, R6 and R10 are each halogen (such as Cl, Br or F), each Cl-Cg-alkyl, or each halogen-substituted C1-C3-alkyl, for example perfluorinated C1-C3-alkyl (perfluoromethyl, perfluoroethyl or perfluoropropyl).
A further red embodiment relates to compounds of the formula (I) in which T is T2, T3, T4, T22, T23 or T46, B3 is C-R8 and R8 is a (Cl—C6)-alkyl, )-alkoxy or alkylsulphanyl, each of which is substituted, where the substituents are ed from halogen and hydroxyl, where at least one substituent is halogen, more preferably in which R8 is perfluorinated (C1-C6)-alkyl, (Cl-C6)-alkoxy or alkylsulphanyl, most preferably perfluorinated (Cl-C4)—alkyl, (Cl—C4)-alkoxy, in which B1, B2 and B4 are, respectively, CR6, CR7 and CR9 and B5 is N, in which R6, R7 and R9 are each ndently H, halogen, cyano, nitro, or C1-C4—alkyl, cycloalkyl, C1—C4—alkoxy, N—alkoxyiminoalkyl, C1-C4— alkylsulphanyl, C1-C4—alkylsulphinyl, C1-C4—alkylsulphonyl, N—Cl-C4-alkylamino, N,N-di—C1-C4— alkylamino, each of which is substituted by at least one substituent selected from halogen and hydroxyl, where at least one tuent is a halogen, each R11 is independently H, amino (NH2) or cyano, preferably H, W is O, R1 is H, , ethyl, n—propyl, isopropyl, n—butyl, isobutyl, s—butyl, t—butyl, preferably H or methyl, Q is C1-C4—alkyl, 2-0X0(2,2,2-trifluoroethylamino)ethyl, fluorine- or 1— \V0 2015/067647 PC’JC/EPZGI4/07379S cyanopropyl— or pyridine—substituted C1—C4-alkyl such as 2,2,2-t1‘ifluoroethyl, 2,2-difluoroethyl, 3,3,3- tiifluoropropyl, pyridin—Z-ylmethyl or (l-cyanocyclopropyl)methyl; C3-C4—cycloalkyl such as cyclopropyl or cyclobutyl; ally substituted C3-C4-cycloalkyl such as optionally e— substituted C1-C4-alkyl-substituted cyclopropyl (e.g. uoromethylcyclopropyl, l-tert— butylcyclopropyl), 1-thiocarbamoylcyclopropyl, l-carbamoylcyclopropyl, ocyclopropyl, trans yclopropyl, cisfluorocyclopropyl; C4-C6—heterocycloalkyl such as oxetanyl, thietan—3-yl, 1- oxidothietanyl, or 1,1-dioxidothietan—3-yl; or in each case ally C1-C4-alkyl-substituted benzyl; pyrazole (such as N—methylpyrazolyl), pyridine; methylsulphonyl; or 2-oxo—2-(2,2,2— trifluoroethylamino)ethyl, preferably fluorine-substituted C1—C3-alkyl such as 2,2,2-trifluoroethy1 or 3,3,3-trifluoropropy1; cyclopropyl; optionally substituted ropyl such as l-cyanocyclopropyl or 1— trifluoromethylcyclopropyl, thietan—3—yl; or 2—oxo(2,2,2—trifluoroethyl)aminoethyl, and all the other parameters are as defined in paragraph [9].
A further preferred embodiment relates to compounds of the formula (I) in which T is T2, T3, T4, T22, T23 or T46, B3 is C—R8 and R8 is a (Cl-C6)—alky1, (C1—C6)-alkoxy or alkylsulphanyl, each of which is tuted, where the substituents are selected from halogen and hydroxyl, where at least one substituent is halogen, more preferably in which R8 is perfluorinated (C1-C6)—alkyl, (Cl-C6)-alkoxy or alkylsulphanyl, most preferably perfluorinated (C1-C4)—alkyl, (C1-C4)-alkoxy, in which B1, B2, B4 and B5 are, tively, CR6, CR7, CR9 and CR10 in which R6, R7, R9 and R10 are each independently H, halogen, cyano, nitro, or C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-alkoxy, N—alkoxy-iminoalkyl, C1-C4- alkylsulphanyl, C1-C4-alkylsulphinyl, C1-C4-alkylsulphonyl, N—Cl-C4-alkylamino, N,N-di-C1—C4- alkylamino, each of which is substituted by at least one substituent selected from n and hydroxyl, where at least one substituent is a halogen, each R11 is independently H, amino (NT-12) or cyano, ably H, W is O, R1 is H, methyl, ethyl, n—propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, preferably H or methyl, Q is C1—C4-alkyl, 2-oxo(2,2,2-triflu0roethyl-amino)ethyl, fluorine- or 1— cyanopropyl- or ne-substituted C1-C4-alkyl such as 2,2,2-trifluoroethyl, 2,2—difluoro-ethyl, 3,3,3— trifluoropropyl, pyridinylmethyl or nocyclopropyl)methyl; C3-C4-cycloalkyl such as cyclopropyl or utyl; optionally substituted cycloalkyl such as optionally fluorinesubstituted Cl-C4-alkyl-substituted cyclopropyl (e.g. 1-trifluoromethylcyclopropyl, 1—tert-butylcyclo- propyl), 1-thiocarbamoylcyclopropyl, l—carbamoylcyclopropyl, l-cyanocyclopropyl, trans-2—fluoro- cyclopropyl, cisfluorocyclopropyl; C4-C6-heterocycloalkyl such as oxetan—3—yl, thietan-3—yl, 1- oxidothietan-3—yl, or 1,1-dioxidothietan—3-yl; or in each case optionally C1-C4—alky1-substituted benzyl; pyrazole (such as N—methylpyrazol—3-y1), pyridine; methylsulphonyl; or 2—oxo—2-(2,2,2- trifluoroethylamino)ethyl, preferably fluorine-substituted alkyl such as 2,2,2-trifluoroethyl or 3,3,3—trifluoropropyl; cyclopropyl; optionally substituted cyclopropyl such as l—cyanocyclopropyl or 1- trifluoromethylcyclopropyl, thietanyl; or 2—oxo(2,2,2-trifluoroethyl)-aminoethyl, A1 is CR2 or N, A2 is CR3 or N, A3 is CR4 and A4 is CR5 or N, where R2 is H, Cl-C4-alkyl or halogen (such as methyl, F, c1 or H), R3 is H or halogenated C1-C4-alkyl (such as H or CE), R4 is H, alkyl, C1-C4- alkylamine (such as —NH-CH3), cyclopropylamine, Cl—C4—alkoxy (such as —O—CH3), C1—C4-alkoxy—Cl— - 161 — ‘5 C4-alkylamine (such as -CHj-O-CHg) or halogen (such as F or Cl). In a further preferred embodiment, R6 and R10 are each halogen (such as Cl, Br or F), each Cl—C3—alkyl, or each halogen- substituted Cl-Cg-alkyl, for example perfluorinated Cl—C3—alkyl (perfluoromethyl, perfluoroethyl or perfluoropropyl).
A further preferred ment relates to compounds of the formula (I) in which T is T2, T3, T4, T22, T23 or T46, B3 is C-R8 and R8 is a (C1—C6)-alkyl, (C1-C6)-alkoxy or alkylsulphanyl, each of which is tuted, where the substituents are selected from halogen and hydroxyl, where at least one substituent is halogen, more preferably in which R8 is perfluorinated (C1-C6)—a1kyl, (C1-C6)-alkoxy or alkylsulphanyl, most preferably perfluorinated (C1-C4)-alkyl, (Cl-C4)-alkoxy, in which B1, B2 and B4 are, respectively, CR6, CR7 and CR9 and B5 is N, in which R6, R7 and R9 are each ndently H, halogen, cyano, nitro, or Cl-C4-alkyl, C3—C4-cycloalkyl, alkoxy, N—alkoxyiminoalkyl, Cl-C4- alkylsulphanyl, Cl—C4-alkylsulphinyl, Cl-C4-alkylsulphonyl, N—Cl-C4-alkylamino, N,N-di-C1-C4- alkylamino, each of which is substituted by at least one substituent selected from halogen and hydroxyl, where at least one substituent is a n, each R11 is independently H, amino (NHZ) or cyano, preferably H, W is O, R1 is H, methyl, ethyl, n-propyl, isopropyl, n—butyl, isobutyl, s-butyl, t-butyl, ably H or methyl, Q is Cl-C4-alky1, 2—oxo—2—(2,2,2-trifluoroethylamino)ethyl, fluorine— or 1— cyanopropyl- or pyridine-substituted Cl—C4-alkyl such as 2,2,2-trifluoroethyl, 2,2-difluoroethy1, 3,3,3- ropropyl, pyridiny1methyl or (l-cyano-cyclopropyl)methyl; C3-C4—cycloalkyl such as cyclopropyl or cyclobutyl; ally substituted cycloalkyl such as optionally fluorine- 2O substituted Cl-C4-alkyl-substituted cyclopropyl (e.g. l~trifluoromethylcyclopropyl, l-tert— butylcyclopropyl), carbamoylcyclopropyl, l-carbamoyl-cyclopropyl, l—cyanocyclopropyl, trans fluorocyclopropyl, cis-2—fluorocyclopropyl; C4-C6-hetero-cycloalkyl such as oxetan-3—yl, thietan—3-yl, 1- hietanyl, or 1,1-dioxidothietanyl; or in each case optionally Cl-C4-alkyl-substituted benzyl; pyrazole (such as N-methylpyrazolyl), pyridine; methylsulphonyl; or 2-oxo-2—(2,2,2- trifluoroethylamino)ethyl, preferably fluorine—substituted alkyl such as 2,2,2-trifluoroethyl or 3,3,3-trifluoropropyl; cyclopropyl; optionally tuted cyclopropyl such as l-cyanocyclopropyl or 1- trifluoromethylcyclopropyl, thietan—3 ~yl; or 2—oxo(2,2,2—trifluoroethyl)aminoethyl, A1 is CR2 or N, A; is CR3 or N, A3 is CR4 and A4 is CR5 or N, where R2 is H, Cl-C4-alky1 or halogen (such as methyl, F, C1 or H), R3 is H or halogenated Cl—C4-alkyl (such as H or —CF_~,), R4 is H, Cl—C4-alkyl, C1—C4-alkylamine (such as —NH-CH3), cyclopropylamine, C1—C4-alkoxy (such as —O—CH3), C1-C4—alkoxy-C1-C4- alkylamine (such as NH-CHz-CHZ-O-CHg) or halogen (such as F or C1).
In a further preferred embodiment, R6 is perfluorinated Cl-C3-alkyl (e.g. perfluoromethyl) and R10 is Cl, Br or F, more preferably C1 or Br.
Formula (Ia") A further preferred embodiment relates to compounds of the formula (Ia’ ’) W0 2015/067647 — 102 - PC’l‘/EPZOl4/O73-795 R // " 3 B\ \\\ D2. 4\[35 D(Ili/D1 0‘;A A1‘/ \4 W A2§A Ga") R1/ Q in which one D selected from D1 and D2 is N and the respective other D selected from D1 and D2 is O; or D4 is N and one D selected from D1 and D5 is N; or D3 is N and D1, D2 and D5 are each C-Rll and D4 is C, and all other parameters are as defined in paragraph [12].
A further preferred embodiment relates to compounds of the formula (Ia") in which R8 is a (C1-C6)- alkyl, (C1-C6)-alkoxy or alkylsulphanyl, each of which is substituted, where the substituents are ed from n and hydroxyl, where at least one substituent is halogen, and one D selected from D1 and D2 is N and the respective other D selected from D1 and D2 is O; or D4 is N and one D ed from D1 and D5 is N; or D3 is N and D1, D2 and D5 are each C-Rll and D4 is C, and all other parameters are as defined in paragraph [12].
In a preferred embodiment, not more than one (1) B1 to B 5 moiety is N (in other words: one (1) B1 to B5 is N); or no (0) B1 to B5 is N (B1 to B5 are CR6, CR7, CR8, CR9 and CRIO).
In a further preferred embodiment, R6, R7, R9 and R10 (if the corresponding B moiety is CR) are each independently H, halogen, cyano, nitro, in each case optionally substituted C1—C4-alkyl, C3-C4- cycloalkyl, C1-C4-alkoxy, N—alkoxyiminoalkyl, C1—C4-a1kylsulphanyl, C1-C4-a1ky1sulphinyl, C1-C4- alkylsulphonyl, N—Cl-C4-alky1amino, N,N—di—C1-C4-a1kylamino.
In a further preferred embodiment, R6, R7, R9 and R10 are each independently H, halogen, cyano, nitro, methyl, ethyl, ethyl, difluoromethyl, chlorodifluoromethyl, trifluoromethyl, 2,2,2- trifluoroethyl, methoxy, ethoxy, n—propoxy, l-methylethoxy, fluoromethoxy, difluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2,2- difluoroethoxy, pentafluoroethoxy, N—methoxyiminomethyl, ethoxyimino)ethy1, methylsulphanyl, romethylsulphanyl, methylsulphonyl, methylsulphinyl, trifluoromethylsulphonyl, trifluoromethylsulphinyl.
In a further preferred embodiment, R6 and R10 are each independently H, halogen (especially chlorine, bromine, fluorine), cyano, nitro, methyl, ethyl, omethyl, difluoromethyl, romethyl, methoxy, ethoxy, 1-methylethoxy, difluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 2—chloro—2,2-difluoroethoxy, "’0 2015/067647 — 163 - methylsulphanyl, trifluoromethylsulphanyl, methylsulphonyl, methylsulphinyl, trifluoromethylsulphonyl, trifluoromethylsulphinyl.
In a further preferred ment, R6 and R10 are the substituents described herein, but R6 and R10 in one compound are not both H. In other words, if R6 in a nd is H, R10 is one of the other substituents described herein, and Vice versa.
In a r preferred embodiment, R6 and R10 are each a substituent selected from halogen (preferably Cl, Br or F), C1-C3—alkyl, halogen-substituted C1—C3—alkyl, alkoxy or halogen- tuted alkoxy.
In a further preferred embodiment, R6 and R10 are each halogen (such as Cl, Br or F), each C1- C3-alkyl, or each halogen-substituted Cl-C3—alkyl, for example perfluorinated alkyl (perfluoromethyl, perfluoroethyl or perfluoropropyl).
In a fidrther preferred ment, R6 is perfluorinated C1-C3-alkyl (e.g. perfluoromethyl) and R10 is Cl, Br or F, more preferably C1 or Br.
T46 — methyl id="p-552" id="p-552" id="p-552" id="p-552" id="p-552" id="p-552"
[552] A further preferred embodiment relates to nds of the formula (I) in which R1 is methyl, T is T46, R11 in T46 is H, W is O and all the other ters are as defined in paragraph [85] and paragraph [0113] ff.
A further preferred embodiment relates to compounds of the formula (I) in which R1 is methyl, T is T46,R11 in T46 is H, w is 0, A1 is CR2, A2 is CR3 or N, A3 is CR4, A4is CR5, B1 is CR6, 32 is CR7, B3 is CR8, B4 is CR9, B5 is CR10 and all the other parameters are as defined in paragraph [85] and paragraph [0113] ff.
A further preferred embodiment relates to compounds of the formula (I) in which R1 is methyl, T is T46,R11 in T46 is H, w is 0, A1 is CH, A2 is CH or N, A3 is CR4,A41s CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CRIO, where R6 and R10 are each a substituent selected from halogen (preferably chlorine, bromine or fluorine), C1-C3-alkyl, halogen—substituted C1-C3-alkyl, C1-C3-alkoxy or halogen- substituted C1-C3-alkoxy and all the other parameters are as defined in paragraph [85] and paragraph A further preferred embodiment relates to compounds of the formula (I) in which R1 is methyl, T is T46,R11 in T46 is H, Wis 0, A1 is CH, A2 is CH or N, A3 is CR4, A4is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CR"), where R6 and R10 are each a substituent selected from halogen (preferably chlorine, bromine or fluorine), C1-C3-alky1, halogen-substituted C1-C3-alky1, C1—C3—alkoxy or halogen- substituted C1—C3-alkoxy and all the other ters are as defined in paragraph [85] and paragraph ‘W0 HITS/067647 — 164 — PCT/EPZUl4/O73795 T46 - H A r preferred ment relates to compounds of the formula (I) in which R1 is H, T is T46, R11 in T46 is H, W is O and all the other parameters are as defined in paragraph [85] and paragraph [01 12].
A further preferred embodiment relates to compounds of the formula (I) in which R1 is H, T is T46,R11 in T46 is H, w is 0, A1 is CR2, A2 is CR3 or N, A3 is CR4, A4is CR5, B1 is CR6, B2 is CR7, B3 is CR8, B4 is CR9, B5 is CR10 and all the other parameters are as defined in paragraph [85] and paragraph A further preferred embodiment relates to compounds of the formula (I) in which R1 is H, T is T46,R11 in T46 is H, w is 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CRIO, where R6 and R10 are each a substituent selected from halogen (preferably chlorine, e or fluorine), C1—C3—alkyl, halogen—substituted alkyl, C1-C3—alkoxy or halogen— substituted C1—C3-alkoxy and all the other ters are as defined in paragraph [85] and paragraph id="p-559" id="p-559" id="p-559" id="p-559" id="p-559" id="p-559"
[559] A further preferred embodiment relates to compounds of the formula (I) in which R1 is H, T is T46, R11 in T46 is H, W is 0, A1 is CH, A2 is CH or N, A3 is CR4, A4 is CH, B1 is CR6, B2 is CH, B3 is CR8, B4 is CH, B5 is CRIO, where R6 and R10 are each a substituent selected from halogen (preferably chlorine, bromine or fluorine), C1-C3-alkyl, halogen-substituted C1—C3-alkyl, C1—C3-alkoxy or halogen- substituted C1-C3-alkoxy and all the other ters are as defined in paragraph [85] and paragraph id="p-113" id="p-113" id="p-113" id="p-113" id="p-113" id="p-113"
[0113] ff.
A further embodiment is directed to nds of the formula ): (I-T46) in which R1, A1, A2, A3, A4, R11, B1, B2, B4, B5, R8, R11 Q and W are each defined as described herein, where not more than one moiety selected from A1, A2, A3, A4 is N and not more than one moiety selected from B1, B2, B3, B4 and B5 is N; or where one or two moieties selected from A1, A2, A3, A4 can be N and not more than one moiety selected from B1, B2, B3, B4, and B5 is N. "’0 2015/067647 — 165 - A further embodiment is directed to compounds of the formula (I—TZ), (I—T3), (I-T4), ), (I- T23) or (l—T46) in which R], A], A2, A3, A4, R", B], B3, B4, B5, R8, Q and W are each as described in paragraph [0120].
A further embodiment is ed to compounds of the a (I—T2), (I—T3), (I-T4), (I-T22), (I-T23) or (I—T46) in which R1, A1, A2, A3, A4, R", B1, B2, B4, B5, R8, Q and W are each as described in paragraph [0121].
A further preferred embodiment is ed to compound D—la D-la id="p-564" id="p-564" id="p-564" id="p-564" id="p-564" id="p-564"
[564] A further embodiment is directed to the use of the compound D—la for preparation of nds of the a (I).
A further embodiment is directed to a process for preparing a compound of the formula (I), preferably in which T = T4, comprising the use of the compound D-1 a, preferably in a reaction sequence according to Reaction Scheme 4. id="p-566" id="p-566" id="p-566" id="p-566" id="p-566" id="p-566"
[566] A r embodiment is directed to compound D—1b D—lb A r embodiment is directed to the use of the compound D-lb for preparation of compounds of the formula (I). id="p-568" id="p-568" id="p-568" id="p-568" id="p-568" id="p-568"
[568] A further embodiment is directed to a process for preparing a compound of the formula (I), preferably in which T = T4, comprising the use of the compound D-1b, preferably in a reaction sequence according to Reaction Scheme 4.
A further embodiment is directed to compound D-lc "’0 2015/067647 — 166 - D-lc A further embodiment is directed to the use of the compound D—lc for ation of compounds of the formula (I). id="p-571" id="p-571" id="p-571" id="p-571" id="p-571" id="p-571"
[571] A flirther embodiment is directed to a process for preparing a compound of the formula (1), preferably in which T = T4, comprising the use of the compound D-lc, preferably in a reaction sequence according to Reaction Scheme 4.
A further embodiment is directed to the compound 2-(3,5~dichlorohydrazinopheny1)- 1,1,1,3,3 ,3-hexafluoropropan—2—ol. id="p-573" id="p-573" id="p-573" id="p-573" id="p-573" id="p-573"
[573] A further embodiment is ed to the use of the nd 2-(3,5-dichloro-4—hydrazino- pheny1)-1,l,1,3,3,3-hexafluoropropan—2-ol for ation of nds of the formula (I).
A further embodiment is directed to a process for preparing a compound of the formula (1), preferably in which T = T4, comprising the use of the compound 2-(3,5-dichlorohydrazino-pheny1)- 1,1,l,3,3,3-hexafluoropropan-2—ol, preferably in a reaction sequence according to Reaction Scheme 4.
V40 67647 — 167 - ‘73795 1,.)[Ir‘1‘inlr 31:1 1. lireparation proce_ss I—"LZ e I-T2—1 F + F F 710 mg (2.24 mmol) of 1-[2,6-dimethyl[1,2,2,2-tetrafluoro—1- (trifluoromethyl)ethy1]phenyl]ethanone were added to 401 mg (3.36 mmol) of N,N-dimethy1formamide dimethyl acetal, and the e was heated to reflux for 5 hours. For workup, the mixture was cooled a little and all the volatile constituents were evaporated off on a rotary evaporator under reduced pressure.
The residue was chromatographed using a cartridge containing 40 g of silica gel with a gradient in cyclohexane/ethyl acetate of 90:10 to 50:50 (v/v). 675 mg of 3-(dimethy1amino)[2,6—dimethy1 [1 ,2,2,2-tetrafluoro-1 -(trifluoromethyl)ethy1]pheny1]propen—1~one were obtained. id="p-576" id="p-576" id="p-576" id="p-576" id="p-576" id="p-576"
[576] 1.2 g (3.23 mmol) of 3—(dimethylamino)[2,6—dimethy1[1,2,2,2—tetrafluoro (trifluoromethyl)ethy1]pheny1]propenone were added to 15.5 ml of ethanol, and 170 mg (3.39 mmol) of hydrazine hydrate and 192 mg (3.2 mmol) of glacial acetic acid were added. The mixture was d at room temperature for 7 hours. Then a filrther 170 mg (3.39 mmol) of hydrazine hydrate were added and the mixture was stirred at room temperature for a further 4 hours. Since the conversion was still incomplete, another 190 mg (3.2 mmol) of glacial acetic acid were added and the mixture was stirred at 60°C for 17 hours. For workup, the mixture was trated on a rotary evaporator under reduced pressure and the e was partitioned between ethyl acetate and water. The organic phase was removed, washed with water, dried with sodium sulphate and concentrated on a rotary evaporator under d pressure. As residue, 1.04 g of (3—[2,6-dimethy1—4-[1,2,2,2-tetrafluoro (trifluoromethyl)ethy1]pheny1]-1H—pyrazole remained. "’0 2015/067647 — 168 — 2014/07379S F\,-F 0 F\[\F, 9H 3 F /——-\ \r / . O F> CI F F N‘N F/ 23 ml of dichloromethane, 353 mg (4.46 mmol) of pyridine, 609 mg (3.35 mmol) of copper(II) acetate, 958 mg (4.46 mmol) of 3-carboxymethylchlorophenylboronic acid and 760 mg (2.23 mmol) of (3-[2,6-dimethyl[l,2,2,2-tetrafluoro(trifluoromethyl)ethyl]phenyl]-lH—pyrazole were initially charged and then 1.1 g of freshly ground 3 A molecular sieve were added. The mixture was then stirred at room temperature for 20 hours. For workup, the mixture was d through a layer of kieselguhr and washed through with dichloromethane. The filtrate was concentrated on a rotary evaporator under reduced pressure. For purification, chromatography was ed first using a cartridge ning 40 g of silica gel with a gradient in cyclohexane/ethyl acetate of 95:5 to 75:25 (V/v). The product—containing fractions were concentrated and chromatographed using a second cartridge containing 40 g of silica gel with toluene as eluent. After concentration, 628 mg of methyl 2-chloro—5-[3-[2,6-dimethyl-4—[1,2,2,2- tetrafluoro-l-(trifluoromethyl)ethyl]phenyl]pyrazolyl]benzoate were obtained.
Li—OH ——> 609 mg (1.19 mmol) of methyl 2-chloro-5—[3-[2,6-dimethyl-4—[1,2,2,2-tetrafluoro (trifluoromethyl)ethyl]phenyl]pyrazol-l-yl]benzoate were initially charged in a mixture of 14 ml of dioxane and 5 ml of water, 53 mg (1.25 mmol) of lithium hydroxide hydrate were added and the mixture was stirred at room temperature. After 2 hours, a r 25 mg (0.6 mmol) of lithium hydroxide hydrate were added and the mixture was stirred at room temperature for a further hour. Thereafter, the volatile constituents were removed on a rotary evaporator under reduced pressure. The residue was partitioned between dilute hydrochloric acid and dichloromethane. The c phase was removed and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were then washed with saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. As e, 554 mg of 2—chloro[3-[2,6-dimethyl—4-[l,2,2,2- uoro—l-(trifluoromethyl)ethyl]phenyl]pyrazol—1-yl]benzoic acid were obtained. 100 mg (0.2 mmol) of 2-chloro—5-[3-[2,6-dimethyl-4—[1,2,2,2-tetrafluoro-l- oromethyl)ethyl]phenyl]pyrazolyl]benzoic acid were initially charged in 2 ml of dry toluene, ‘ — 169 — PCT/EP2014/G73795 then 120 mg (1 mmol) of thionyl chloride (SOC12) and 1 drop of dimethylformamide (DMF) were added, and the mixture was heated to reflux. After the evolution of gas had ended, the mixture was d under reflux for another 30 minutes and then concentrated on a rotary evaporator under d pressure. The residue was dissolved in 1 ml of dry dichloromethane and added dropwise to a solution of 29 mg (0.5 mmol) of cyclopropylamine in 1 ml of dichloromethane at 0°C. The mixture was then d at room temperature for 2 hours. For workup, the mixture was poured onto 5% aqueous sodium hydrogencarbonate solution, and the organic phase was removed, washed with saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated on a rotary evaporator under reduced 40 g of silica gel pressure. For ation, chromatography was effected using a cartridge containing with a gradient in cyclohexane/ethyl acetate of 90:10 to 50:50 (v/v). 159.5 mg of 2-chloro-N— ropyl—S -[3 -[2,6-dimethyl[l ,2,2,2—tetrafluoro-l -(trifluoromethyl)ethyl]phenyl]pyrazol-l - yl]benzamide (compound I-T2-1) were obtained.
S‘": logP = 4.9, mass (m/Z) = 534 [M+H]+. 1H NMR (400 MHz, d3-acetonitrile): 5 (ppm) = 8.29 (d, J=2.5 Hz, 1 H), 7.82-7.85 (m, 2H), 7.52 (d, J=8.8 Hz, 1 H), 7.44 (s, 2 H), 6.97 (s (broad), 1 H (N—H)), 6.54 (d, J=2.5 Hz, 1 H), 2.82—2.86 (m, 1H), 0.74—0.79 (m, 2 H), 0.59-0.61 (m, 2 H).
Preparation of the starting compounds: id="p-580" id="p-580" id="p-580" id="p-580" id="p-580" id="p-580"
[580] 271 mg (11.1 mg atom) of ium turnings were initially charged, covered with a little dry tetrahydrofuran and, after addition of a few drops of a solution of 3 g (8.49 mmol) of 2-bromo-l,3- dimethyl-S — [l ,2,2,2-tetrafluoro-l -(trifluoromethyl)ethyl]benzene (prepared ing to /187233, p. 6, Example 2/4 [0080]) in 10 ml of dry tetrahydrofuran, a crumb of iodine was added. To start the reaction, the mixture was heated to 60°C. After the reaction had started up, the rest of the solution containing the 2-brom0-1,3-dimethyl—5-[l,2,2,2-tetrafluoro (trifluoromethyl)ethyl]benzene was added dropwise at 60°C. After the addition had ended, the mixture was stirred at 60°C for another hour. Thereafter, the e was cooled to 0°C with an ice bath, and 1.86 g (25.4 mmol) of N,N—dimethy1formamide, dissolved in 5 ml of dry tetrahydrofuran, were added dropwise. Then the mixture was stirred without cooling until the e had reached room temperature.
For workup, the mixture was poured onto saturated aqueous ammonium chloride solution. The phases were separated; the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with ted aqueous sodium chloride solution, dried with sodium sulphate and concentrated "’0 2015/067647 — 170 — on a rotary evaporator under reduced pressure. As residue, 2.34 g of 2,6-dimethyl—4-[1,2,2,2—tetrafluoro- l-(trifluorometliyl)ethyl]benzaldehyde remained, which was used t purification in the next stage.
+ MeMgl —-> 2.34 g (7.74 mmol) of 2,6-dimethyl[l,2,2,2-tetrafluoro (trifluoromethyl)ethyl]benzaldehyde were initially charged in 15.5 ml of dry tetrahydrofuran, and 2.58 ml (7.74 mmol) of a 3 M solution of methylmagnesium iodide in diethyl ether were added dropwise while cooling with an ice bath. Subsequently, the mixture was stirred without cooling for a further hour.
For workup, the mixture was poured onto 100 ml of saturated aqueous um chloride solution.
The mixture was extracted twice with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried with sodium sulphate and trated on a rotary evaporator under reduced pressure. The residue was chromatographed using a 40 g cartridge containing silica gel with a gradient in cyclohexane/ethyl acetate of 90:10 to 70:30 (v/v), and gave 1.0 g of l-[2,6- dimethyl—4-[l ,2,2,2-tetrafluoro-1 -(trifluoromethyl)ethyl]phenyl]ethanol.
+ MnO2 ——> [5 82] 1.49 g (4.68 mmol) of -dirnethyl[1,2,2,2-tetrafluoro—1- (trifluoromethyl)ethyl]phenyl]ethanol were initially charged in 84 ml of toluene, and 10.8 g (124 mmol) of manganese(IV) oxide were added. The mixture was heated to reflux while stirring for one hour. This was followed by g, filtering through a layer of kieselguhr and washing through with ethyl acetate.
The e was concentrated on a rotary evaporator under reduced re. The residue was chromatographed using a cartridge containing 50 g of silica gel with a gradient in cyclohexane/ethyl acetate of 95:5 to 70:30 (v/v). 1.03 g of -dimethyl[1,2,2,2-tetrafluoro-l— (trifluoromethyl)ethyl]phenyl]ethanone were obtained.
WC) 2015/067647 - 171 — l’C’l'/E1)2014/073795 e I-T3-1: The preparation of the precursor [2,6—dimethy1—4—[1 ,2,2,2-tetrafluoro (trifluoromethyl)ethyl]pheny1]hydrazine is described in the literature (US 2003/ 1 8723 3).
E: I / Q FF 0 o FF + F FF \Ey/O\ F o\ FFF A 25 ml flask was initially d with 3.41 g (11.2 mmol) of [2,6-dimethyl-4—[1,2,2,2- tetrafluoro-l-(trifluoromethyl)ethyl]phenyl]hydrazine (free base) in 13 ml of ethanol. Then 1.84 g (11.2 mmol) of tetramethoxypropane and subsequently 0.55 g (5.6 mmol) of 96% sulphuric acid were added.
The reaction mixture was heated to reflux for 2 h. Ethanol was ated off on a rotary evaporator under reduced pressure. The residue was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution. The organic phase was removed, dried with sodium te and concentrated on a rotary evaporator under reduced pressure. The residue was distilled in a Kugelrohr under d pressure at 1 mbar and 150°C, and gave 2.5 g of l—[2,6—dimethy1—4—[1,2,2,2-tetrafluoro-l- (trifluoromethyl)ethyl]phenyl]pyrazole.
N / N / | F F F F + 0410 ——> FF ’1' FF F/FF F/ F A 250 ml flask was initially charged with 2.5 g (7.34 mmol) of 1—[2,6—dimethyl—4-[1,2,2,2- tetrafluoro-l-(trifluoromethyl)ethyl]phenyl]pyrazole in 30 ml of acetonitrile, and 8.3 g (36.9 mmol) of N—iodosuccinimide in 50 ml of acetonitrile were added se. Subsequently, the mixture was heated to reflux. For workup, the mixture was concentrated, and the residue was partitioned between water and \VO 2015/067647 — 172 — 2014/073795 ethyl acetate. The organic phase was removed, washed first with saturated aqueous sodium hydrogensulphite solution, then with saturated sodium chloride solution, dried with sodium sulphate and concentrated. The residue was purified by tography with silica gel by means of a gradient from 90:10 to 70:30 (v/v) in exane/ethyl acetate. After concentration of the fractions containing the product, 2.5 g of a residue were obtained, which consisted of 1-[2,6-dimethyl—4-[l,2,2,2-tetrafluoro (trifluoromethyl)ethyl]phenyl]—4-iodopyrazole and some toluene.
F F (PH 0 F F I Cl F_ \N/ + Pd(0)(PPh3)4 —> N \ o F F ‘N~ \ F o id="p-586" id="p-586" id="p-586" id="p-586" id="p-586" id="p-586"
[586] A 100 ml flask was initially charged with 280 mg (0.6 mmol) of 1—[2,6-dimethyl[l,2,2,2- tetrafluoro-l~(trifluoromethyl)ethyl]phenyl]~4-iodopyrazole and 0.129 g (0.60 mmol) of [4-chloro-3— (methoxycarb0nyl)phenyl]boronic acid in 21 ml of isopropanol, and lastly 1.84 ml (1.84 mmol) of degassed 1 molar sodium hydrogencarbonate solution were added. 0.035 g (0.03 mmol) of tetrakis(triphenylphosphine)palladium(0) was added. Then the mixture was heated to reflux. For workup, the mixture was concentrated on a rotary evaporator, and the residue was partitioned n water and ethyl acetate. The organic phase was removed, washed once with ted sodium chloride on and concentrated on a rotary evaporator under reduced pressure. The e was purified by chromatography with silica gel by means of a gradient from 90:10 to 70:30 (v/v) in cyclohexane/ethyl acetate, and gave 151 mg of methyl 2-chlor0-5—[1-[2,6-dimethyl[l,2,2,2—tetrafluoro-l— (trifluoromethyl)ethyl]phenyl]pyrazolyl]benzoate.
F F Cl Cl F \ F \ / \ F N O\ + Na-OH ——> \N. \ 0H F F F N_ F N— [5 87] 0.151 g (0.29 mmol) of methyl 2—chloro[l-[2,6-dimethyl[l,2,2,2-tetraflu0r0-1— (trifluoromethyl)ethyl]phenyl]pyrazolyl]benzoate were initially charged in 11 ml of methanol, and 0.3 ml (0.3 mmol) of 1M sodium hydroxide solution were added. Subsequently, the mixture was heated to reflux for 6 hours, excess solvent was evaporated under reduced pressure, and the residue was taken up with dilute hydrochloric acid and ted three times with ethyl acetate. The combined ts were washed with saturated sodium chloride solution, dried with sodium sulphate and concentrated, and gave 130 mg of 2-chloro[1-[2,6—dimethyl[l,2,2,2-tetrafluor0—l— (trifluoromethyl)ethyl]phenyl]pyrazolyl]benzoic acid. ‘ - 173 — F F F FF F / /C| - \ F H \ 0:8,Cl Q N \ N OH + + .
F ‘N‘ él H2N F N‘ O OI—x 0.134 g (0.27 mmol) of 2-chloro[1-[2,6-dimethyl[1,2,2,2—tetrafluoro—1- (trifluoromethyl)ethy1]phenyl]pyrazoly1]benzoic acid were dissolved in 1.26 ml of toluene, and 0.161 heated to 80°C for 2 hours. This was g (1.35 mmol) of l chloride were added. The e was followed by concentration under reduced pressure. The residue was dissolved in 1.26 ml of dichloromethane and added dropwise to a solution of 39 mg (0.67 mmol) of ropylamine in 0.63 ml of dichloromethane at 0°C while g, and the solution was cooled. For workup, 5% aqueous sodium dihydrogenphosphate solution was added, and the organic phase was removed, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. The residue was separated with silica gel with a gradient of cyclohexane/ethyl acetate of 9:1 to 7:3 (v/v), and gave 46 mg of 2-chloro—N—cyclopropyl-5 -[ 1 -[2,6—dimethyl[1 ,2,2,2-tetrafluoro-1 ~ (trifluoromethyl)ethyl]pheny1]pyrazo1-4—y1]benzamide und ).
HPLC-MSa): logP = 4.36, mass (m/z) = 534 [M+H]+. 1H NMR (400 MHz, d3—acetonitrile): 5 = 8.11 (s, 1 H), 8.06 (s, 1 H), 7.68 (d, J1=2.2 Hz, 1 H), 7.62-7.65 (dd, J1=8.4 Hz, J2=2.2 Hz, 1H), 7.45 (d, J=8.4 Hz, 1 H), 6.9 (s (broad), 1 H (N-H)), 3.97 (s, 3 H), 2.82- 2.88 (m, 1H), 0.76—0.8 (m, 2 H), 0.57-0.61 (m, 2 H).
Examples I—T3-48 and IT-T3-50 _N\ 0L IL / 11‘ \ N N O \ NJfiOH 0" F I / F + Na-OH I + I: FX / / F \Cl Cl F Cl F F/\F \0/ 2.46 g (5.9 mmol) of methyl 2—chloro[1-[2,6-difluoro—4-(trifluoromethyl)phenyl]pyrazol y1]benzoate were initially charged in 127 ml of methanol, and 5.9 mg (5.9 mmol) of 1 molar sodium hydroxide solution were added. The mixture was heated to reflux for 2 hours. Thereafter, the mixture was cooled, and the majority of the methanol was removed on a rotary evaporator under reduced pressure. The aqueous residue was extracted with dichloromethane. extract was discarded. The aqueous phase was set to pH 1 with 33% hydrochloric acid and ted twice with dichloromethane.
The combined extracts were washed with saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated. 1.41 g of residue were ed as a 45:55 (LC—MS areas) mixture of 2— —5—[1-[2,6-difluoro—4-(trifluoromethyl)phenyl]pyrazoly1]benzoic acid and 2—chloro—5—[l-[2- fluoromethoxy(trifluoromethyl)pheny1]pyrazolyl]benzoic acid.
\’\"O 67647 - 174 — " rdflow * @3969)? / F F C' CI F F F /0 700 mg (about 1.7 mmol) of a 45:55 (LC-MS areas) mixture of 2-chloro[1-[2,6-difluoro (trifluoromethyl)phenyl]pyrazolyl]benzoic acid and 2-chloro-5 -[1 - romethoxy (trifluoromethyl)phenyl]pyrazol—4-y1]benzoic acid were dissolved in 6.6 m1 of toluene, and 1.34 g (8.7 mmol) of thionyl chloride were added. The mixture was heated to 80°C for 2 hours. Thereafter, all the volatile constituents were drawn off on a rotary evaporator under reduced pressure. The residue was dissolved in 3.3 ml of dichloromethane and added dropwise to a on of 248 mg (4.34 mmol) of cyclopropylamine in 3.3 ml of dichloromethane at 0°C. The mixture was then stirred without cooling for 2 hours. Thereafter, the solution was washed with 5% aqueous sodium dihydrogenphosphate solution, dried with sodium sulphate and concentrated. The residue was chromatographed using a cartridge ning 40 g of silica gel with a gradient in cyclohexane/ethyl acetate of 90:10 to 50:50 (v/v). 240 mg of 2-chloro-N—cyclopropyl—5 —[1 —[2,6—difluoro(trifluoromethyl)phenyl]pyrazoly1]benzamide (Example I-T3-48) Sa): logP = 3.2, mass (m/z) = 442 [M+H]+. 1H NMR (400 MHz, d3-acetonitrile): 6 (ppm) = 8.26 (s, 1 H), 8.19 (s, 1H), 7.61-7.69 (m, 4H), 7.46 (d, J = 8.3 Hz, 1H), 6.94 (s, 1 H (broad)), 2.82—2.88 (1n, 1H), 0.75-0.80 (m, 2 H), 0.58-0.62 (m, 2 H). and 2—chloro-N—cyclopropy1—5 ~[1 -[2-fluoro—6-methoxy—4-(trifluoromethyl)phenyl]pyrazol-4— y1]benzamide (Example I—T3—50) were obtained.
HPLC—MSa): logP = 3.1, mass (m/z) = 454 [M+H]+. 1H NMR (400 MHZ, d3—acetonitrile): 8 (ppm) = 8.13 (s, 1 H), 8.11 (s, 1H), 7.67 (d, J = 2.2 Hz, 1 H), 7.62 (dd, J1= 8.3 Hz, J; = 2.2 Hz, 1 H), 7.45 (d, J = 8.3 , 7.32 (s, 1 H), 7.30 (s, 1 H), 6.91 (s, 1H (broad)), 3.90 (s, 3 H), 2.83-2.87 (m, 1H), 0.75-0.79 (m, 2 H), 0.57-0.61 (m, 2 H).
Example I-T3-121: o N CI OH CI N Y OH | 045.01 I __, \f/ o/\ N\ + \ +/ N C| 0' \ ' — 175 - S 4.6 ml (49.6 11111101) of phosphoms oxychloride were initially charged and 1.3 g (7.44 mmol) of —cl1lorooxo—1H—pyrimidine-6—earboxylic acid (commercially available, or can be prepared by methods known from the literature (e. g. Gacek, Michel; Ongstad, Leif; Undheim, Kjell; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry B33(2), (1979), p. 150-1)) were introduced. The mixture was heated gradually and kept under reflux for 2 hours. Thereafter, the mixture was cooled a little and the excess phosphorus oxychloride was drawn off on a rotary evaporator under reduced pressure. 20 ml of dry ethanol were added to the residue, and the mixture was then stirred at room temperature overnight. fter, excess ethanol was drawn off on a rotary evaporator under reduced pressure. The residue was taken up in dichloromethane and washed three times with ted were re-extracted with aqueous sodium hydrogencarbonate on. The aqueous phases dichloromethane, then the combined organic phases were washed with saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated on a rotary evaporator under d pressure. The residue was chromatographed using a cartridge ning g of silica gel with a gradient from pure cyclohexane to 50:50 (v/v) exane/ethyl acetate, and gave 115 mg of ethyl 2,5- dichloropyrimidinecarboxy1ate.
‘B’O 1 an a +M$ .
+ LI—Cl + 013,0 F N\N CI 6 F \ FF A out 25 m1 three-neck flask was initially charged with 5.94 ml (7.72 mmol) of a 1.3 molar solution of i-propylmagnesium chloride/lithium chloride complex, and a solution of 4-iodo[2- methyl[1 ,2,2,2-tetrafluor0-1 -(trifluoromethy1)ethy1](trifluoromethyl)pheny1]pyrazole (for preparation see Example ) in 3.4 m1 of dry tetrahydrofuran was added dropwise. Stirring of the mixture at room temperature continued overnight, and then the mixture was cooled to -20°C and 1.63 g (10.2 mmol) of 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane were added dropwise. The mixture was d at 0-10°C for a r 1 hour. For workup, the mixture was poured onto 30 ml of ted s ammonium chloride solution and diluted with cyclohexane. The phases were separated; washed first with aqueous phase was re-extracted with cyclohexane. The combined organic phases were saturated aqueous sodium hydrogencarbonate solution and then with saturated s sodium chloride solution, dried with sodium sulphate and concentrated on a rotary evaporator under reduced re.
After chromatography using a 40 g cartridge containing silica gel with a gradient proceeding from pure cyclohexane up to 80:20 (V/V) cyclohexane/ethyl acetate, 0.6 g of 1-[2,6-dimethy1[1,2,2,2~tetrafluoro- 1-(trifluoromethy1)ethy1]pheny1]—4-(4,4,5,5-tetramethy1—1,3,2-di0xaborolan—2-y1)pyrazole was obtained.
V90 2015/067047 — 176 — 2014/073795 O8-84 r N\ \g‘fio _/ 0 Ifil = N N/j_ Cl N /\ _/ o F / O F .4 / —> / I— if + + Pd(0)(PPh3)4 F F IN 155 mg (0.7 mmol) of ethyl 2,5-dichloropyrimidinecarb0xylate and 327 mg (0.7 mmol) of [2,6—dimethyl[1 ,2,2,2-tetrafluoro-1 —(trifluoromethyl)ethyl]phenyl](4,4,5,5—tetramethyl—l ,3 ,2- dioxaborolanyl)pyrazole were initially charged in 25 ml of dioxane and 234 mg (2.2 mmol) of sodium carbonate and 1.25 ml of water were added. The mixture was degassed with argon and then 81 added. The mixture was degassed mg (0.07 mmol) of tetrakis(triphenylphosphine)palladium(0) were the e was cooled and the once again with argon and stirred at 100°C overnight. The next morning, solvent was drawn off on a rotary evaporator under reduced re. The residue was partitioned between water and ethyl acetate. The organic phase was removed, washed once with saturated aqueous sodium chloride solution and then concentrated on a rotary evaporator under reduced pressure. For purification, chromatography was effected using a cartridge containing 15 g of silica gel and a gradient proceeding from pure cyclohexane as far as a mixture of 70:30 (v/V) cyclohexane/ethyl acetate. 120 mg of ethyl 5-chloro[l-[2,6-dimethyl—4—[l,2,2,2-tetrafluoro-1—(trifluoromethyl)ethyl]phenyl]pyrazol yl]pyrimidine—4-carboxylate were obtained. 0.120 g (0.23 mmol) of ethyl 5-chloro[1-[2,6-dimethyl[1,2,2,2—tetrafluoro—l— (trifluoromethyl)ethyl]phenyl]pyrazolyl]pyrimidine—4-carboxylate were initially charged in a e of 4.1 ml of dioxane and 1.44 ml of water, and 31 mg (0.74 mmol) of lithium hydroxide monohydrate 4 hours, then excess solvent were added. Subsequently, the mixture was stirred at room ature for dilute hloric acid was evaporated off under reduced pressure, and the residue was taken up with and extracted three times with dichloromethane. The combined ts were washed with saturated sodium sulphate and concentrated, and gave 115 mg of aqueous sodium chloride solution, dried with crude 5-chloro[l -[2,6-dimethyl[1 -tetrafluoro-1 -(trifluoromethyl)ethyl]phenyl]pyrazol yl]pyrimidinecarboxylic acid. ' — 177 - 0.110 g (0.22 mmol) of crude ro[1—[2,6-dimethyl[1,2,2,2-tetrafluoro-l- (trifluoromethyl)ethyl]phenyl]pyrazol—4—yl]pyrimidine—4~carboxy1ic acid were dissolved in 2 ml of toluene, and 0.132 g (1.1 mmol) of thionyl chloride and one drop of dimethylformamide were added.
The mixture was heated to 80°C for 2 hours. This was followed by concentration under reduced re. The residue was dissolved in 1 m1 of dichloromethane and added dropwise to a on of 32 mg (0.55 mmol) of cyclopropylamine in 1 ml of dichloromethane at 0°C while cooling, and the mixture was then stirred without cooling for 2 hours. For workup, 5% aqueous sodium dihydrogenphosphate solution was added, and the organic phase was removed, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. The residue was separated using a cartridge containing g of silica gel with a gradient of cyclohexane/ethyl e of 9:1 to 7:3 (v/v), and gave 49 mg of 5- -N—cyclopropyl-Z-[l —[2,6-dimethyl[l ,2,2,2-tetrafluoro-l -(trifluoromethyl)ethy1]phenyl]pyrazol- 4-yl]pyrimidinecarboxamide (compound I-T3-121).
HPLC-MSa): logP = 4.5, mass (m/z) = 536 [M+H]+. 1H NMR (400 MHz, d3-acetonitrile): 8 (ppm) = 8.84 (s, l H), 8.46 (s, 1 H), 8.44 (s, 1H), 7.87 (s, 1 H (broad)), 7.55 (s, 2 H), 2.84-2.91 (1n, 1 H), 2.2 (s, 6 H), 0.79—0.83 (m, 2 H), .68 (m, 2 H).
Example I-T3-134: F F 4%! —* '15 /_\_..
To a e, cooled to 0°C, of 6.5 mg (0.163 mmol) of sodium hydride (60% in mineral oil) in 2 ml of dry tetrahydrofuran were added 49.3 mg (0.08 mmol) of 2-chloro-N-cyclopropyl-5—{l-[4- (1,1 , l ,2,3,3,3-heptafluoropropany1)—2—(trifluoromethyl)pheny1]—1H-pyrazol—4-yl}benzamide. After 30 minutes, 35 mg (0.24 mmol) of methyl iodide were added, and the e was stirred at 0°C and for 1 hour, then warmed up to room temperature over the course of 1 hour and stirred at room temperature for a further 14 hours. Thereafter, the mixture was added to water and extracted with ethyl acetate, the organic phase was dried over sodium sulphate and the solvent was removed under reduced pressure. The W0 2015/067647 — 178 — PCT/13112014073795 e was purified by chromatography on reversed-phase silica gel (C 18) with water/acetonitrile (gradient) as eluent. 40.0 mg (0.068 mmol, 78%) of 2—chloro—N—cyclopropyl—S—[5-[2,6-dichloro—4- [l ,2,2,2-tet1‘afluoro-1 —(trifluoromethyl)ethyl]phenyl]isoxazol—3-yl]benzamide (compound I—T3-134) were obtained.
HPLc—Msa): logP = 4.88, mass (m/z) = 588 [M+H]+. 1H NMR (400 MHz, dé-DMSO): 5 (ppm) = 8.82 (s, 1 H), 8.43 (s, 1 H), 8.25 (d, 1H), 8.11 (d, 1 H), 8.06 (d, 1 H), 7.81 (d, 1 H), 7.75 (m, 1 H), 7.54 (d, 1 H), 3.02 (s, 3 H), 2.72 (m, 1 H), 0.55 (m, 2 H), 0.46 (m, 2 H).
Example 56: [5 97] 2—Chloro—N—cyclopropyl { l -[3 -(ethylsulphanyl)(l ,1 ,1 ,2,3 ,3 ,3 -heptafluoropropan—2- yl)pyridin—2—yl] -lH-pyrazol—4-yl}benzamide Ni \ Q \/S / N F F F <—F F F F 2-(4-Br0mo-1H—pyrazol—1—yl)chloro(1,1,1,2,3,3,3-heptafluor0propanyl)pyridine 1.0 g (3.16 mmol) of 2,3-dichloro—5-(1,l,1,2,3,3,3—heptafluoropropan—2-y1)pyridine were added dropwise to a suspension of 0.51 g (3.48 mmol) of 4-bromo—lH-pyrazole and 2.58 g (7.91 mmol) of caesium carbonate in 10.0 ml of dimethylformamide p.a. The reaction was stirred at room temperature for 3 h. The reaction mixture was then diluted with ethyl e and then washed with semisaturated aqueous ammonium chloride solution. The aqueous phase was then extracted repeatedly with ethyl acetate, and the combined organic phases were subsequently washed with distilled water and saturated sodium chloride on. The organic phase was dried over magnesium sulphate, filtered and concentrated on a rotary evaporator under reduced pressure. The crude product was d by column chromatography on silica gel.
This gives 1.34 g (3.14 mmol) of 2-(4-bromo-lH—pyrazol—1—y1)chloro-5—(l,1,l,2,3,3,3- heptafluoropropanyl)pyridine as a colourless oil.
HPLC—MSa): logP = 4.74, mass (m/z) = 428 . 1H NMR (400 MHZ, D6-DMSO): 8.90 (s, 1H), 8.67 (s, 1H), 8.63 (d, 1H), 8.06 (s, 1H). ‘ - 179 — Z-Chloro-S—{l-[S-Chlor'o—S-(l,1,I,2,3-,3,3—lieptafiuoropropan-Z-yl)pyridin~2—yl]-1H—pyrazolyi}-N- cyclopropylbenzamide 150 mg (0.35 mmol) of 2-(4-bromo-lH—pyrazol-l—y1)chloro—5-(1,1,1,2,3,3,3- heptafluoropropan—2—yl)pyridine, 136 mg (0.42 mmol) of 2-Chloro-N-cyclopropyl-5~(4,4,5,5- tetramethyl—l,3,2-dioxaborolan—2-yl)benzamide, 59 mg (0.70 mmol) of sodium encarbonate and mg of tetrakis(triphenylphosphine)palladium (0.01 mmol) were dissolved in a mixture of 1.5 m1 of dioxane and 0.5 ml of distilled water. The solvents were saturated with argon for about 30 minutes prior to use, by passing argon gas through the ts. The reaction mixture was heated in an oil bath to 100°C for 16 hours. After the reaction e had been cooled to room temperature, the mixture was admixed with water and the crude t was extracted repeatedly with ethyl acetate. The combined organic phases were dried over magnesium sulphate and filtered through silica gel. The solvents were removed on a rotary ator under reduced pressure. The crude product was purified by colurrm chromatography on silica gel.
This gave 25 mg (0.05 mmol) of 2-chloro-5—{1—[3-chloro(1,1,l,2,3,3,3-heptafluoropropan—2- yl)pyridinyl]-1H—pyrazol—4-y1}-N-cyclopropylbenzamide as a colourless solid.
HPLC-MS"): logP = 4.08, mass (m/z) = 541 [M+H]+. 1H NMR (400 MHz, D6-DMSO): 9.02(s,1H), 8.89(s,1H), 8.61(d,1H), 8.54—8.52(m,1H), 8.50(s,1H), 7.83-7.81(m,2H), 7.52(d,1H), 2.87-2.81(m,1H), 0.74—0.65(m,2H), 0.60-0.50(m,2H) 2—Chloro-N-cyclopropyl—S-{1-[3-(ethylsulphanyl)—5-(l,1,1,2,3,3,3-heptaflu0r0propan—2—yl)pyridin— 2-yl]-1H-pyrazol—4-yl}benzamide 300 mg (0.55 mmol) of 2—chloro{l-[3-chloro(1,1,1,2,3,3,3-heptafluoropropan yl)pyridin—2-yl]~1H—pyrazolyl}-N—cyclopropy1benzamide were dissolved in 5.0 m1 of DMF abs. and cooled with a dry ice/acetone bath. To the cooled reaction mixture was added se a solution of 81.6 mg (0.97 mmol) of sodium ethanethiolate in 5 ml of DMF abs. After 3 hours, the on mixture was warmed up to room temperature and poured cautiously onto water. The crude product was extracted repeatedly with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulphate and filtered, and concentrated on a rotary evaporator under d pressure. The crude product was d by column chromatography on silica gel.
This gives 226 mg (0.40 mmol) of 2-chloro-N—cyclopropyl—5-{1-[3-(ethylsulphanyl) (l,1,1,2,3,3,3-heptafluoropropanyl)pyridinyl]-lH-pyrazolyl}benzamide as a colourless solid.
HPLC—MSa): logP = 4.69, mass (m/z) = 567 [M+H]+. 1H NMR (400 MHz, D6—DMSO): 9.08 (d, 1H), 8.59 (d, 1H), 8.53 (d, 1H), 8.47 (s, 1H), 8.02 (d, 1H), .82 (m, 2H), 7.53—7.50 (m, 1H), 3.08 (q, 2H), 2.87-2.81 (m, 1H), 1.22 (t, 3H), 0.74-0.69 (m, 2H), 0.58-0.54 (m, 2H). — 180 - PCT/EP2014/O73795 Example I—T3-157: 2-Chl0r0-N—cyclopropyl-S-{1-[3-(ethylsulphi11yl)-5—(1,1,1,2,3,3,3-heptaflu0ropropan-2—yl)pyridin- 1H-pyrazol—4—yl}benzamide \/\( id="p-604" id="p-604" id="p-604" id="p-604" id="p-604" id="p-604"
[604] 100 mg (0.17 mmol) of 2-chloro—N—cyclopropyl—5—{1-[3-(ethylsulphany1)(l,1,1,2,3,3,3— heptafluoropropan-Z-yl)pyridin—2-yl]-1H—pyrazolyl}benzamide were dissolved in 10.0 ml of dichloromethane and cooled with an ice bath. 43.5 mg of 3-chloroperbenzoic acid were added in portions. The on mixture was stirred while cooling with ice for 2 hours. The reaction mixture was admixed with 5 m1 of 1N sodium hydroxide solution. After 5 minutes, the aqueous phase was removed.
After checking for peroxides, the organic phase was trated on a rotary evaporator under reduced pressure. The crude product was purified by column tography on silica gel.
This gave 61 mg of Z-Chloro—N-cyclopropyl-S-{1-[3-(ethy1su1phiny1)(1,1,1,2,3,3,3— heptafluoropropan—2—yl)pyridin—2-yl]—1H-pyrazol—4-y1}benzamide as a colourless solid.
HPLC-MSa): logP = 379, mass (m/z) = 583 [M+H]+. 1H NMR (400 MHZ, D6—DMSO): 9.36 (s, 1H), 8.96 (d, 1H), 8.63 (s, 1H), 8.58 (s, 1H), 8.53 (d, 1H), 7.91 (s, 1H), 7.89 (d, 1H), 7.53 (d, 1H), 3.45—3.30 (m, 1H beneath water), 2.95-2.88 (m ,1H), 2.86-2.81 (m, 1H), 1.08 (t, 3H), 0.74—0.69 (m, 2H), .50 (m, 2H).
Preparation of the starting compounds 2,3-Dichloro—5—(1,1,1,2,3,3,3-heptafluoropropan—Z-yl)pyridine F F F F \VO 2015/067647 - 181 — 1st stage: 3—Chlor0(1,l,l,2,3,3,3—lieptafiudreproparr—Z—g/Dpyrldin—Z-amine 130.6 g (750 mmol) of sodium dithionite were added to a mixture, cooled to 0-5°C, of 64.3 g (500 mmol) of 3-chloropyridinamine, 222 g (750 mmol) of 2,3,3,3—heptafluoroiodopropane and 126 g (1500 mmol) of sodium hydrogencarbonate in 2000 ml of a 3:1 mixture of acetonitrile/water (V/V) under protective gas. The reaction mixture was stirred at room temperature for 48 hours. The acetonitrile was then removed on a rotary evaporator under reduced pressure. The residue was diluted with 500 ml of water. The crude product was extracted repeatedly from the aqueous phase with ethyl acetate. The ed organic phases were dried over sodium sulphate, filtered and then concentrated on a rotary evaporator under reduced pressure. The crude product was purified by column chromatography on silica gel. 2nd stage: 3-Chloro(1,1,1,2,3,3,3-heptafluoropropan—2-yl)pyridin-2(1H)—one id="p-607" id="p-607" id="p-607" id="p-607" id="p-607" id="p-607"
[607] 5.8 g (19.5 mmol) of 3—chloro(l,l,1,2,3,3,3-heptafluoropropan—2-yl)pyridinamine were dissolved in 150 ml of sulphuric acid (20%, w/w) and cooled to 0-5°C. The on was admixed with 2.7 g (40 mmol) of sodium nitrite in portions. The reaction mixture was stirred at room ature for 16 hours. The crude product was extracted repeatedly from the reaction mixture with dichloromethane (DCM). The combined organic phases were dried over sodium te, filtered and then concentrated on a rotary evaporator under reduced pressure. The crude product was used in the next stage without purification. 3rd stage: chlor0(1,1,1,2,3,3,3-heptafluoropropan—2—yl)pyridine id="p-608" id="p-608" id="p-608" id="p-608" id="p-608" id="p-608"
[608] 15.4 g (51.7 mmol) of 3-chloro—5—(l,l,1,2,3,3,3—heptafluoropropan—2—yl)pyridin-2(1H)-one and 150 ml of phosphoryl chloride were heated to 105°C for 5 hours. The reaction mixture was neutralized cautiously with sodium hydrogencarbonate solution. The crude product was extracted repeatedly from the reaction mixture with DCM. The combined organic phases were washed with saturated s sodium chloride solution, dried over sodium sulphate and filtered, and then trated on a rotary evaporator under reduced pressure. The t was provided by vacuum distillation (b.p. 40°C at 1 mbar) .
This gave 14.8 g of 2,3-dichloro-5—(1,l,l,2,3,3,3—heptafiuoropropan-2—yl)pyridine as a colourless liquid.
MS: mass (m/z) = 315 [M]+. 1H NMR (400 MHz, dl—chloroform): 8.48 (s, 1H), 7.95 (s, 1H).
\VO 2015/06764‘7 , 182 .. PCT/EP‘2014/07379S Example I—T3-161: F F\/F /O. / F F F F F F F \F I F F\\ \ .,-C| \ IE-S F / \ .c| F: é_|'3 —‘>F_ \ /\N \ I \ / H \ H F N + F F \ I; \_ _ F ‘ r V S / N I/N O S \ / \7 294 mg (0.5 mmol) of 2-chloro-N-cyc10propyl-5~[1-[2-methy1-4~[1,2,2,2-tetrafluoro (trifluoromethyl)ethyl](trifluoromethyl)phenyl]pyrazolyl]benzamide were initially charged in a mixture of 0.5 ml of ethanol—free trichloromethane and 1.5 m1 of 1,2-dimethoxyethane, and 101 mg (0.25 mmol) of Lawesson's reagent (2,4—bis(4-methoxyphenyl)—1,3,2,4-dithiadiphosphetane 2,4- disulphide) were added. The e was heated to 50°C for 4 hours. Thereafter, the mixture was cooled and the solvent was drawn off on a rotary evaporator under reduced pressure. The residue was partitioned n ethyl e and saturated aqueous sodium hydrogencarbonate solution; the dried with aqueous phase was re-extracted once with ethyl acetate. The combined organic phases were sodium te and concentrated on a rotary ator under d pressure. For purification, chromatography was effected using a cartridge containing 40 g of silica gel with a gradient in cyclohexane/ethyl acetate of 90:10 to 50:50 (WV). 248 mg of 2—chloro-N—cycIopropyl[1—[2—methy1—4- [1 ,2,2,2-tetrafluoro-1 —(trifluoromethyl)ethy1]-6—(trifluoromethy1)phenyl]pyrazol y1]benzenecarbothioamide (compound I-T3-161) were obtained.
HPLC-MS"): logP = 5.0, mass (m/z) = 604 [M+H]+. 1H—NMR (400 MHZ, d3-acetonitrile): 5 (ppm) = 8.62 (s, l H (broad)), 8.14 (s, 1 H), 8.10 (s, 1H), 8.0 (s, 1 H), 7.95 (s, 1 H), 7.63 (d, J=2.2 Hz, 1 H), 7.57-7.60 (m, 1 H), 7.42 (d, J=8.4 Hz, 1 H), 3.02 (s, 3 H), 3.37-3.44 (m, 1 H), 0.92-0.95 (m, 2 H), 0.74-0.78 (m, 2 H).
Preparation l.)_xpccss_l-_'l‘_4 e I—T4-1: id="p-611" id="p-611" id="p-611" id="p-611" id="p-611" id="p-611"
[611] 3.81 g (12.2 mmol) of ethyl 2—ch10ro-5—iodobenzoate were initially charged in 37 m1 of dimethylformamide, and 2.885 g (19.6 mmol) of 4—bromopyrazole, 5.09 g (36.8 mmol) of freshly ground potassium carbonate, 0.349 g (2.4 mmol) of 1,2-bis(methylamino)cyclohexane (racemic, trans) and 0.234 g (1.22 mmol) of copper(I) iodide were added. The mixture was degassed with argon and then \’\7O 2015/067647 - 18(.4) heated to reflux for one hour. For workup, the mixture was cooled, poured onto 100 ml of water and extracted twice with 100 ml each time of ethyl acetate. The combined organic phases were washed twice with 100 ml of water and then with saturated sodium chloride solution, dried with sodium sulphate and trated on a rotary evaporator under reduced pressure. For purification, the residue was chromatographed using a 120 g dge containing silica gel with a gradient of cyclohexane/ethyl acetate of 90:10 to 70:30 (v/v). 1.41 g of ethyl romopyrazoly1)—2-chlorobenzoate were obtained. 44 .0? + Mg(0) 0‘ ,O F , F O\ FI—E/ F 0.158 g (6.49 mg) of magnesium turnings were covered with 1.5 ml of dry tetrahydrofuran. A few drops of a solution of 1.75 g (4.95 mmol) of 2-bromo-1,3-dimethy1—5-[1,2,2,2—tetrafluoro (trifluoromethyl)ethyl]benzene (prepared according to U82003/187233, p. 6) in 2.5 ml of dry tetrahydrofuran were added. To start the reaction, a crumb of iodine was added and the e was heated to about 55°C. After the reaction had started, the remaining on of the 2-bromo-1,3- dimethyl-5—[1,2,2,2—tetrafluoro—1-(triflu0romethy1)ethyl]benzene was added dropwise at a temperature of 55°C. After the addition had ended, stirring was continued at 55°C for another 1 hour, then the mixture was cooled to 0°C and a solution of oxy-4,4,5,5-tetramethy1—1,3,2-dioxaborolane in 2.5 m1 of dry tetrahydrofuran was added se. Then the mixture was allowed to come to room temperature. For workup, the mixture was poured onto saturated aqueous ammonium chloride solution.
The phases were separated, the s phase was re-extracted with ethyl acetate, then the ed organic phases were washed with saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. The residue was distilled in a Kugelrohr at a vacuum of 1 mbar and 220°C. 1.85 g of 2-[2,6—dimethyl-4—[1,2,2,2—tetrafluoro—1- (trifluoromethyl)ethyl]phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane were obtained. r / \ .F N i F \ O + F 1 + Pd(Ph3P)4 —> / Noo _N Y \/ id="p-613" id="p-613" id="p-613" id="p-613" id="p-613" id="p-613"
[613] 0.947 g (2.87 mmol) of ethyl 5-(4-bromopyrazol—1—y1)—2-chlorobenzoate and 1.15 g (2.87 mmol) of 2—[2,6-dimethyl-4—[ 1 ,2,2,2-tetrafluoro-1—(triflu0romethyl)ethyl]phenyl]—4,4,5 ,5-tetramethyl-1 ,3 ,2- orolane were initially charged in 62 m1 of isopropanol, and 8.7 ml (8.7 mmol) of degassed 1 molar aqueous sodium hydrogencarbonate solution were added. The mixture was degassed with argon \NO 2015/067647 - 184 — PCT/EPZUI4/073795 and 0.166 g (0.14 11111101) of 1etrakis(triphenylphosphi11e)palladiu111(0) were added and the mixture was heated to reflux ght.
For workup, the mixture was concentrated on a rotary evaporator under d pressure, and the residue was ioned between water and ethyl e. The organic phase was removed; the The combined organic phases were then washed once aqueous phase was re-extracted with ethyl acetate. with saturated aqueous sodium chloride solution and concentrated on a rotary evaporator under reduced pressure. As residue, 1.17 g of crude ethyl 2-chloro[4-[2,6-dimethyl-4—[l,2,2,2-tetrafluoro-l- (trifluorornethyl)ethyl]phenyl]pyrazolyl]benzoate were obtained.
F F F F F\ F F F / N o + Na-OH ———> / N OH I \/ F I F F F _N —N O O id="p-615" id="p-615" id="p-615" id="p-615" id="p-615" id="p-615"
[615] 1.76 g (3.36 mmol) of ethyl 2-chloro[4-[2,6-dimethyl[1,2,2,2-tetrafluoro-1— (trifluoromethyl)ethyl]phenyl]pyrazolyl]benzoate were initially charged in 72 ml of methanol, and 4.03 ml (4.03 mmol) of 1 molar sodium hydroxide solution were added. The mixture was then heated to reflux for 3 hours. For workup, the mixture was concentrated on a rotary evaporator under reduced acid and extracted three times with ethyl re, and the residue was taken up with dilute hydrochloric acetate. The combined extracts were washed with saturated sodium de solution, dried with sodium sulphate and concentrated, and gave 1.36 g of crude 2—chloro—5~[4-[2,6—dimethyl[1,2,2,2—tetrafluoro- 1-(triflu0romethyl)ethyl]phenyl]pyrazol-l —yl]benzoic acid.
FF F: F Cl / Cl F'43? / \I \ ——> / / /OH + 0:3’Cl A_ Fiif {‘1 + p ./ \ / n F 0’ H7N E ‘ F F N _N o \/ 1.36 g (2.76 mmol) of crude 2-chlor0[4-[2,6-dimethyl—4-[1,2,2,2—tetrafluoro-l- (trifluoromethyl)ethyl]phenyl]pyrazol-1—yl]benzoic acid were dissolved in 14 ml of dry toluene, 1 ml (13.8 mmol) of thionyl chloride was added and then the e was heated to 80°C for 2 hours.
Thereafter, the mixture was concentrated on a rotary evaporator under reduced pressure, 1 ml of dry toluene was added and the mixture was trated again. 1.4 g of crude acid chloride were obtained as residue. 0.7 g of the e was dissolved in 5 ml of dichloromethane and added dropwise to a solution of 0.195 g (3.41 mmol) of cyclopropylamine in 2 m1 of romethane at room temperature. The mixture was stirred at room temperature for a further 2 hours, then poured onto 20 ml of 5% aqueous sodium dihydrogenphosphate solution. The organic phase was removed and washed with saturated sodium chloride solution, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. The residue was purified by two chromatography runs using a cartridge containing 15 of 90:10 to 50:50 (v/v). 91 mg (1.36 mmol) g of silica gel with a gradient of cyclohexane/ethyl acetate "’0 2015/067647 — 1 00 5 — P‘CT/E132014/07379S of opropyl—Z-cliloro-5 - 6—dimethyl-4—[l ,2,2,2—tetrafluoro—1 - (trifluoromethyl)ethyl]phenyl]pyrazol—l -yl]benzamide (compound I-T4-1) were obtained.
HPLC—MSa): logP = 4.74, mass (m/z) = 534 [M+H]+. 1H NMR (400 MHZ, tonitrile): 8 = (ppm) 8.17 (s, l H), 7.86 (s, l H), 7.84 (d, J1=2.7 Hz, 1 H), 7.69 (s, l H), 7.54(d, J1=8.8 Hz, 1H), 7.44 (s, 2 H), 6.97 (s (broad), 1 H (N—H)), 2.83—2.87 (m, 1H), 2.25 (s, 6 H), 0.76-0.8 (m, 2 H), 0.58-0.62 (m, 2 H).
Example I-T4-3: F F CNN NA FF \ H \N CI I O H2N’N \ + O/\ / ’0‘ + Na 8 CI —_> I n N Cl \N 2 / 2 g (9.96 mmol) of ethyl 5-aminochloronicotinate rcially available) were initially charged in 8.6 ml of 33% aqueous hydrochloric acid, and the e was stirred at room temperature for 30 minutes. Thereafter, 7 ml of water were added and the mixture was cooled to 0°C with an ice bath. To this mixture was added dropwise a solution of 750 mg (10.8 mmol) of sodium nitrite in 6.92 ml of water within 30 minutes. The temperature was kept below +5°C with an ice bath. Stirring was continued at 0°C for 15 s.
A second flask was initially charged with 5.77 g (25.5 mmol) of tin(II) chloride dihydrate in 24 ml of 16% aqueous hydrochloric acid, and the diazonium salt suspension prepared above was slowly added dropwise at 0°C. Stirring was continued at 0°C for 1 hour. Thereafter, 50 ml of acetonitrile and 40 ml of saturated aqueous sodium chloride solution were added. The phases formed were separated. The The combined organic phases aqueous phase was extracted twice with 50 ml each time of acetonitrile. were dried with sodium sulphate and concentrated on a rotary evaporator under reduced re. The residue obtained was 10.7 g of crude ethyl 2-chlorohydrazinonicotinate.
O l I H O 0 fl 0 ,N L \ H2N {Y O/\ N’N \ O/\ + ((0 \ I N CI / N Cl V170 2015/067647 2014/073795 10.7 g of crude ethyl 2—chloro-5—hydrazinonicotinate were initially charged in 50 ml of ethanol, then 1.63 g (9.92 mmol) of l,l,3,3—tetramethoxypropane and 487 mg of 96% sulphuric acid were added.
The mixture was subsequently heated to reflux for 2 hours. The maj ority of the ethanol was removed on a rotary evaporator under d pressure, and the e was partitioned between saturated s sodium encarbonate solution and ethyl acetate. The organic phase was removed, washed with saturated aqueous sodium chloride solution, dried over sodium sulphate and concentrated on a rotary evaporator under reduced pressure. The residue was chromatographed using a cartridge containing 15 g of silica gel and a nt ding from pure cyclohexane to 50:50 (v/v) cyclohexane/ethyl acetate. 396 mg of ethyl 2-chloro(pyrazol—l -yl)nicotinate were obtained.
O\ O 2% O N Cl I N CI 396 mg (1.57 mmol) of ethyl 2-chloro(pyrazol—1-yl)-nicotinate were initially charged in 10 m1 of acetonitrile, and 1.062 g (4.72 mmol) of N—iodosuccinimide were added. uently, the mixture was heated under reflux under argon for 3 hours. The mixture was cooled a little and the t water was removed on a rotary evaporator under reduced pressure. The residue was partitioned between and ethyl acetate. The organic phase was removed, washed first with saturated aqueous sodium hydrogensulphite solution then with saturated aqueous sodium hydrogencarbonate solution and lastly with saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. The residue was chromatographed using a cartridge containing 15 g of silica gel and a nt proceeding from pure cyclohexane to 50:50 (v/v) cyclohexane/ethyl acetate.
O F 0/\ O / F I l +F + Pd(0)(Ph3P)4 —> \{N - o \/ I \ F __ N / \ F N CI F _ O 401 mg (1.06 mmol) of ethyl 2—chloro(4—iodopyrazol-l-yl)pyridin—3—carboxylate and 425 mg (1.06 mmol) of 2-[2,6-dimethyl[l,2,2,2-tetrafluoro-l-(trifluoromethyl)ethyl]phenyl]-4,4,5,5— tetramethyl—l,3,2—dioxaborolane were lly charged in 23 ml of isopropanol, and 3.24 ml (3.24 mmol) of degassed 1 molar aqueous sodium hydrogencarbonate on and 61 mg (0.05 mmol) of tetrakis(triphenylphosphine)palladium(0) were added. The mixture was degassed once again with argon and heated to reflux overnight. Thereafter, the mixture was cooled and the volatile constituents were drawn off on a rotary evaporator under reduced pressure. The residue was partitioned between water and ethyl acetate. The organic phase was removed, washed once with saturated aqueous sodium chloride solution and concentrated on a rotary evaporator under reduced pressure. 415 mg of crude ethyl 2- ‘NO 2015/067647 - 187 — chloro—5 —[4-[2 , 6 -dimethyl-4— [l ,2,2 ,2—tetrafluoro— 1 -(trifluoromethyl)ethyl]phenyl]pyrazol— 1 -yl]pyridine- oxylate were ed.
—N F F ~N F F \ /\ \ + Na-OH F F \ C' \N CI N F F F F 416 mg (0.79 mmol) of crude ethyl 2-chloro[4-[2,6-dimethyl[1,2,2,2-tetrafluoro-l- (trifluoromethyl)ethyl]phenyl]pyrazolyl]pyridine—3-carboxylate were dissolved in 16.9 ml of methanol, and 0.952 ml (0.95 mmol) of 1 M sodium hydroxide solution was added. The e was heated under reflux for 6 hours, then cooled and concentrated on a rotary evaporator under reduced dilute hydrochloric acid. The aqueous pressure. The residue was partitioned between ethyl acetate and phase was re-extracted twice with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated on a rotary ator under reduced pressure. 380 mg of crude 2-chloro[4-[2,6-dimethy1—4-[l,2,2,2—tetrafluoro~ fluoromethyl)ethy1]phenyl]pyrazoly1]pyridine-3—carboxy1ic acid were obtained. 380 mg (0.76 mmol) of crude 2-chloro—5—[4-[2,6-dimethyl[1,2,2,2—tetrafluoro-l- (trifluoromethyl)ethyl]pheny1]pyrazolyl]pyridinecarboxylic acid were dissolved in toluene, and 456 mg (3.83 mmol) of l chloride were added. The mixture was heated to 80°C for 2 hours and then concentrated on a rotary evaporator under reduced pressure. 400 mg of crude 2—chloro[4—[2,6- dimethyl-4—[1,2,2,2-tetrafluoro-1 -(trifluoromethyl)ethyl]pheny1]pyrazol-1 -y1]pyridine—3-carbonyl chloride were ed.
F \ixl CI / HN "F \ + \ 2W—* "N CI 13 8 mg (0.26 mmol) of 2-chloro—5-[4—[2,6—dimethy1[l,2,2,2-tetrafluoro-l— (trifluoromethyl)ethy1]pheny1]pyrazolyl]pyridine-3—carbonyl chloride were dissolved in 1 ml of dichloromethane and added dropwise to a solution of 38 mg of cyclopropylamine in 1 ml of dichloromethane at room temperature. The mixture was stirred at room temperature for a further 2 hours. Then the mixture was washed with 5% sodium dihydrogenphosphate solution and then with saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. For purification, chromatography was effected using a cartridge — 188 — containing 15 g of silica gel with a gradient in cyclohexane/ethyl e of 90:10 to 50:50 (V/V). 30 mg of 2-chloro-N—cyclopropyl—5 —[4—[2,6-dimethyl[1,2,2,2-tetrafluoro-l— (trifluoromethyl)ethyl]phenyl]pyrazoly1]pyridine—3-carboxamide were obtained.
HPLC-MSa): logP = 4.42, mass (m/z) = 534 [M+H]+. 1H NMR (400 MHz, ds-acetonitrile): 8 (ppm) = 8.92 (d, J = 2.8 Hz, 1 H), 8.22 (d, J1=2.8 Hz, 1 H), 8.20 (s, 1 H), 7.75(s, 1H), 7.44 (s, 2 H), 5.1 (s (broad), 1 H (N-H)), 2.84-2.88 (m, 1H), 2.25 (s, 6 H), 0.78- 0.81 (m, 2 H), 0.59-0.63 (m, 2 H).
Preparation process I-T22 e I-T22-1: Br 0 F F r/ Mm)g + + /N\ F F The preparation of methy1heptafluoroisopropylbromobenzene is described in U82003/187233, p. 6 [0080]. id="p-626" id="p-626" id="p-626" id="p-626" id="p-626" id="p-626"
[626] In a 25 ml three—neck flask, 158 mg (6.5 mg atom) of magnesium gs were covered with dry tetrahydrofuran (THF). Then a few drops of a solution of 1.75 g (4.95 mmol) of 2,6-dimethyl-4— heptafluoroisopropylbromobenzene in 2.5 ml of dry THF were added. To start the reaction, a crumb of iodine was added and the mixture was heated to about 60°C. After the reaction had started, the rest of the solution of the 2,6-dimethy1heptafluoroisopropylbromobenzene was added se at about 60°C. After the addition had ended, stirring was ued at 60°C for another hour, then the mixture was cooled to 0°C and a solution of 1.09 g (14.8 mmol) of dimethylformamide in 2.5 ml of dry THF was added dropwise. Then the mixture was allowed to come to room temperature. For workup, excess saturated aqueous ammonium chloride solution was added, the phases were separated, and the aqueous phase was re—extracted with ethyl acetate. The combined organic phases were washed with ted sodium chloride solution, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. As residue, 1.3 g of crude 2,6—dimethyl—4-heptafluoroisopropylbenzaldehyde (purity about 80%) remained, which were used further t purification.
V170 2015/067647 - 189 — 1.3 g (about 3.44 11111101) of cmde 2,6-di111ethyl—4-heptafluoroisopropylbenzaldehyde were dissolved 111 26 1111 of methanol, 36l 111g (4.3 11111101) of sodium hydrogencarbonate were added and the mixture was cooled to 0°C. Thereafter, 1.2 g (17.2 mmol) of hydroxylammonium chloride were added and the mixture was stirred at room temperature overnight. For , the mixture was trated on a rotary evaporator under reduced pressure, and the residue was taken up in 100 ml of ethyl acetate.
Undissolved constituents were filtered off and the filtrate was concentrated on a rotary evaporator under d pressure. The residue was then purified by chromatography using a 40 g cartridge ning silica and a nt proceeding from pure cyclohexane to 70:30 (v/v) cyclohexane/ethyl acetate. 0.5 g of 2,6-dimethyl-4—heptafluoroisopropylbenzaldehyde oxime was ed. 505 mg (1.59 mmol) of 2,6-dimethyl—4-heptafluoroisopropylbenzaldehyde oxime were initially charged in 3.5 ml of dimethylformamide (DMF), and 234 mg (1.75 mmol) of N—chlorosuccinimide were added. The mixture was stirred at room temperature for 3.5 hours. Then the mixture was cooled to 0°C and a solution of 310 mg (1.59 mmol) of methyl 2-chloro-5—ethynylbenzoate (prepared according to W02012/107434, p. 103) in 1.5 ml of DMF was added dropwise, ed by 355 mg (3.5 mmol) of triethylamine. The reaction mixture was then stirred at room temperature ght. For workup, the mixture was poured onto water and extracted twice with dichloromethane, and the combined extracts were washed with water, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. For purification, purification was effected using a 40 g cartridge containing silica gel and a gradient proceeding from pure cyclohexane to 80:20 (V/v) cyclohexane/ethyl acetate. 488 mg of methyl 2-ch10ro-5 -[3 -[2,6-dimethyl-4—[l ,2,2,2-tetrafluoro-l -(trifluoromethyl)ethyl]phenyl]isoxazol-S — yl]benzoate were ed.
Li—‘OH ———> 0.8 g (1.56 mmol) of methyl 2-chloro—5—[3-[2,6-dimethyl[l,2,2,2—tetrafluoro (trifluoromethyl)ethyl]phenyl]isoxazol-S—yl]benzoate were initially charged in a mixture of 18 ml of dioxane and 6.5 ml of water, 86 mg (2.04 mmol) of lithium hydroxide monohydrate were added and the ‘ mixture was stirred at room temperature overnight. For workup, the mixture was concentrated under reduced pressure and the residue was partitioned between a mixture of dilute hydrochloric acid and dichloromethane. The c phase was removed; the aqueous phase was extracted first with romethane, then with ethyl e. The combined organic phases were washed with saturated and concentrated on a rotary evaporator aqueous sodium chloride solution, dried with sodium sulphate under d pressure. 680 mg of 2—chloro[3—[2,6-dimethyl-4—[1,2,2,2-tetrafluoro (trifluoromethyl)ethyl]phenyl]isoxazol-S—yl]benzoic acid were ed.
F F F F F F F F N\ F F .N\ F o¢S,CI O + / HO CI cu Cl 680 mg (1.37 mmol) of 2-chloro—5-[3-[2,6-dimethyl-4—[l,2,2,2—tetrafluoro (trifluoromethyl)ethy1]phenyl]isoxazol-S-yl]benzoic acid were dissolved in 7 ml of toluene, and 0.5 ml (6.89 mmol) of thionyl chloride were added. The mixture was heated to 80°C for two hours and then concentrated on a rotary evaporator under reduced pressure. 200 mg (0.38 mmol) of the crude acid chloride thus obtained were dissolved in 1 ml of dichloromethane and added dropwise to a solution of 56 mg (0.97 mmol) of ropylamine in 0.95 ml of dichloromethane at room temperature. The mixture was then stirred at room temperature overnight. For workup, the mixture was poured onto 5% the organic phase was removed, dried with sodium aqueous sodium dihydrogenphosphate solution, and sulphate and concentrated on a rotary evaporator under reduced pressure. For purification, the residue was chromatographed using a cartridge containing 15 g of silica gel and a gradient from pure cyclohexane to 80:20 (v/V) cyclohexane/ethyl acetate. 165 mg of ro—N-cyclopropyl[3-[2,6— dimethyl-4—[1,2,2,2—tetrafluoro—l—(trifluoromethyl)ethyl]phenyl]isoxazolyl]benzamide (compound I- T22—1) were ed.
Sa): logP = 4.75, mass (m/z) = 535 [M+H]+. 1H NMR (400 MHZ, d3-acetonitrile): 5 (ppm) = 7.93 (d, J=2.2 Hz, 1 H), 7.89 (dd, J1=8.4 Hz, J2=2.2 Hz, 1H), 7.6 (d, J=8.4 Hz, 1H), 7.49 (s, 2 H), 7.03 (s (broad), 1 H (N—H)), 6.86 (s, 1 H), 2.83—2.88 (m, 1H), 0.75-0.79 (m, 2 H), 0.59—0.62 (m, 2 H).
W0 EMS/067647 - 191 — 2014/073795 Prcmraliou JI'OCCSS 15123 Exam )lc 3-l: F\ \‘ _/ é; ,CI F""'| ' F \I/H\ .0 C! E! N x930_\" N‘i’ j F 0 F F F If [CL \ 2K0 F Cl F l /\/ \ / \/ 1/ Pd‘ —> I F I F $51 P + + + / F / F l Br i \ ¢ C, E: o \?l c: 3 g (7.61 mmol) of 2-bromo-l,3—dichloro-5—[1,2,2,2-tetrafluoro-l- (trifluoromethyl)ethy1]benzene (for preparation see EP 1 253 128, page 10), 1.21 g (12.3 mmol) of ethynyltrimethylsilane, 86 mg (0.38 mmol) of palladium(II) acetate and 260 mg (1.0 mmol) of triphenylphosphine were initially charged in 20 ml of dry triethylamine and heated to reflux. After concentrating the volume on a rotary evaporator at 30°C, the residue was admixed with 20 ml of saturated sodium hydrogencarbonate solution and extracted three times with dichloromethane. The ed extracts were washed with 5% aqueous NaH2PO4 solution and then with saturated sodium chloride solution. After drying the solution with sodium sulphate and trating the volume on a rotary evaporator at 30°C, purification was effected by means of chromatography on silica gel with cyclohexane as . Yield: 1 .4 g of 2—[2,6-dichloro—4-[1 ,2,2,2—tetrafluoro—1 - (trifluoromethyl)ethyl]phenyl]ethynyltrimethylsilane in a purity of about 50% (LC-MS area).
F F F\F F F F C' F CI F F + Li—OH ——» F F F \\ 5’ ¢ Si Cl CI 1.4 g (3.4 mmol) of 2—[2,6-dichlor0—4—[1,2,2,2-tetrafluoro-l— (trifluoromethyl)ethyl]phenyl]ethynyltrimethylsilane were dissolved in 7 m1 of tetrahydrofuran, and a mixture of 7 ml of methanol and 214 mg (5.1 mmol) of lithium hydroxide monohydrate was added at room ature. The reaction solution was concentrated on a rotary evaporator and the residue was taken up with a e of dichloromethane and water. The organic phase was removed, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure, and gave 880 mg of about 50% 1,3—dichloroethynyl—5-[1,2,2,2-tetrafluoro-l-(trifluoromethyl)ethyl]benzene.
V's-70 2015/067647 — 192 — PCT/E1’2014—/073795 The preparation of 4—chlorocarbomethoxybenzaldehyde has already been described in the literature (see, for example, , p. 19-20). 0 o HON o "A"o/ HO O‘Na Il‘--..,=-’-::; z'JL / /_l T 3 [I I O H + HzN-OH HCI + id="p-634" id="p-634" id="p-634" id="p-634" id="p-634" id="p-634"
[634] 4.1 (20.6 mmol) of 4-chloro—3-carbomethoxybenzaldehyde were dissolved in 82 ml of methanol, 1.734 mg (20.6 mmol) of sodium hydrogencarbonate were added and the e was cooled to 0°C. Then 5.738 g (82.5 mmol) of hydroxylamine hydrochloride were added and the mixture was stirred. For workup, the mixture was trated on a rotary evaporator, and the residue was taken up in 100 ml of ethyl acetate. The solids were filtered off and the e was concentrated on a rotary ator under reduced pressure. For purification, the residue was chromatographed with silica gel by means of a nt in 9:1 to 7:3 (V/v) cyclohexane/ethyl acetate, and gave 2.68 g of ethyl 2-chloro [(E)-hydroxyiminomethyl]benzoate.
Ho.IN (11 / Cl C: ('3: 277 mg (1.29 mmol) of ethyl 2-chlor0-5—[(E)—hydroxyimin0methyl]benzoate were lly charged in 4.6 ml of dimethylformamide, 381 mg (2.84 mmol) of N—chlorosuccinimide were added, and the mixture was stirred at room temperature. The mixture was then cooled to 0°C with an ice bath, and a solution of 880 mg (about 50% strength, 1.29 mmol) of 1,3-dichloroethynyl—5-[l,2,2,2-tetrafluoro-l- (trifluoromethyl)ethy1]benzene in 1.5 m1 of dimethylformamide was added dropwise, followed by 289 For workup, the on mg (2.85 mmol) of triethylamine. The mixture was stirred at room temperature. was diluted with water and extracted twice with dichloromethane. The combined extracts were washed with water, dried with sodium sulphate and concentrated on a rotary evaporator. The residue was purified by two chromatography runs on silica with a gradient proceeding from pure cyclohexane to 80:20 (v/v) cyclohexane/ethyl acetate as eluent, and gave 410 mg of methyl 2—chloro—5-[5-[2,6-dichlor0- 4-[1 —tetrafluoro-1 —(trifluoromethyl)ethyl]phenyl]isoxazolyl]benzoate. — 193 — + ’ Na-OH 410 mg (0.74 mmol) of methyl 2-chloro—5-[5-[2,6-dichloro[l,2,2,2-tetrafluoro-l- (trifluoromethyl)ethyl]phenyl]isoxazolyl]benzoate were initially charged in 21 ml of methanol, 0.74 ml (0.74 mmol) of 1M sodium hydroxide solution were added and the mixture was stirred under reflux.
Subsequently, the methanol was d on a rotary evaporator. The residue was admixed with dilute hydrochloric acid and extracted three times with ethyl acetate. The combined extracts were dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. 405 mg of ro—5- [5-[2,6-dichloro[1,2,2,2-tetrafluoro—l-(trifluoromethyl)ethyl]pher1yl]isoxazol—3—yl]benzoic acid were obtained as e.
CI 2 9,),\n, 125 mg (0.23 mmol) of 2-chloro—5—[5-[2,6-dichlor0[l,2,2,2-tetrafluoro-l— (trifluoromethyl)ethyl]phenyl]isoxazolyl]benzoic acid were dissolved in 1.1 ml of dry toluene, and 0.14 g (1.16 mmol) of thionyl chloride was added. The mixture was heated to 80°C and then concentrated on a rotary evaporator. The residue was dissolved in 0.25 ml of dichloromethane and added se to a solution of 33 mg (0.58 mmol) of cyclopropylamine in 0.75 ml of dichloromethane at 0°C, and the mixture was stirred at room ature for 2 hours. For workup, 5% aqueous sodium dihydrogenphosphate solution was added and then the organic phase was removed. The organic phase was dried with sodium sulphate and concentrated on a rotary evaporator. The residue was purified by chromatography with silica gel and 70:30 (v/v) cyclohexane/ethyl acetate as eluent. 49 mg of 2-chloro- opropyl—S -[5-[2,6-dichloro[1 ,2,2,2—tetrafluoro-1 uoromethy1)ethyl]phenyl]isoxazol yl]benzamide (compound I—T23-l) were obtained.
S"): logP = 4.96, mass (m/z) = 575 [M+H]+. 1H NMR (400 MHz, 63666161116116): 5 = 7.96 (s, 1 H), 7.94-7.96 (dd, J1=8.4 Hz, J2=2.2 Hz, 1H), 7.86 (s, 2 H), 7.6 (d, J1=7.6 Hz, J2=1.2, 1 H), 7.15 (s, 1 H), 6.9 (s (broad), 1 H (NH)), 397 (s, 3 H), 2.83- 2.88 (m, 1H), 0.75—0.79 (m, 2 H), 0.58-0.62 (m, 2 H).
VK’O' 67647 - 194 — S Process 1 Example 4-heptafluorois0propyl—Z-methyl-6—trifluoromethylaniline F F + F + HO-OH ——> D-la A three-neck flask was initially charged with 17.48 g (100 mmol) of 2-methy1 trifluoromethylaniline in 498 m1 of dimethyl sulphoxide, and then 44.3 g (21.095 m1, 150 mmol) of 2- iodoheptafluoropropane, 29.9 ml (29.9 mmol) of 1 molar iron(II) sulphate solution in water and 5.43 ml (104 mmol) of 96% sulphuric acid were added. The mixture was then degassed with argon and then a syringe pump was used to add 20.4 ml of 30% aqueous hydrogen peroxide solution dropwise within 15 minutes. The temperature rose to 54°C. Towards the end of the dropwise addition, the mixture was heated briefly to 60°C. The mixture was d for a further 20 minutes without heating, in the course of which the temperature fell to 36°C. For workup, the mixture was poured onto saturated aqueous sodium hydrogencarbonate solution and the t was ted with ethyl acetate. The combined extracts were washed first with water and then with saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. For purification, chromatography was effected in two portions through a column containing 120 g of silica gel and a gradient from pure cyclohexane to 95:5 exane/ethyl e (V/V). 18.9 g of 4- heptafluoroisopropylmethyl-6—trifluoromethylaniline were obtained.
Analogously, 2-chloroheptafluoroisopropyltrifluoromethylaniline was also obtained proceeding from 2-chlorotrifluoromethylaniline and 2—iodoheptafluoropropane: F F NH2 l + F + HO-OH —> Cl F F A three—neck flask was initially charged with 30 g (0.153 mol) of 2—chloro trifluoromethylaniline (commercially available) in 765 ml of dimethyl xide (DMSO), and then 68.1 g (0.23 mol) of 2-iodoheptafluoropropane, 46 ml of a 1 molar aqueous iron(II) sulphate solution and 15.4 g of 98% sulphuric acid were added. The mixture was degassed with argon and then a syringe pump was used to add 34.8 g of 30% aqueous hydrogen peroxide solution dropwise within 30 minutes.
In the course of this, the temperature rose to 70°C. The mixture was stirred for a further 20 s, in the course of which the temperature fell to 30°C. The reaction mixture was then poured onto saturated aqueous sodium hydrogencarbonate on and ted with ethyl acetate. The combined extracts ‘WQ 2015/067647 — 195 — were washed first with water, then with ted aqueous bisulphite solution and saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. For purification, cln'omatography was effected using a cartridge containing 330 g of silica gel and a gradient proceeding from pure cyclohexane to 90:10 (v/v) cyclohexane/ethyl acetate. 46.1 g of 2—chloroheptafluoroisopropyltrifluor0methylaniline were obtained.
Process 2 Example 4-heptaflu0roisopropyl—Z-methyl—6-trifluoromethylaniline F 2 :: O-Na + F+s; + Fe(l|)SO4 +HO-O F F O F F D-1a id="p-641" id="p-641" id="p-641" id="p-641" id="p-641" id="p-641"
[641] In a 1000 ml three-neck flask, 25 g (91 mmol) of 4-heptafluoroisopropyl-Z-methylaniline were added to a mixture of 363.4 ml of water and 181.7 ml of acetonitrile. Then 27.3 ml (27.3 mmol) of aqueous 1 molar iron(II) sulphate solution and 31.19 g (200 mmol) of sodium trifluoromethylsulphinate were added. The mixture was ted with argon and then 35.1 g (273 mmol) of a 70% aqueous tert- butyl eroxide on were metered in with a syringe pump within 4.5 hours without cooling.
The temperature rose to 34°C. After the addition had ended, stirring was continued for another 1 hour.
For workup, the e was poured onto 425 ml of ted aqueous sodium hydrogensulphite solution and stirred for 15 minutes. Then 425 ml of ted sodium hydrogen carbonate solution were added and the mixture was extracted three times With ethyl acetate. The combined organic phases were washed first with water and then with saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated on a rotary ator under reduced pressure. The crude product was chromatographed in two portions using a cartridge containing 120 g of silica gel and a cyclohexane/ethyl acetate nt of 95:5 to 85:15 (V/V). 19.5 g of 4-heptafluoroisopropy1-2—methyl trifluoromethylaniline were obtained.
HPLC-MS"): logP = 4.67 GC/MS: mass (m/z) = 343, retention time: 2.98 min, Kovats index: 1089 (Agilent 6890 GC, HP5979 MSD, 10m DB—l, iD=0.18mm, FILM=0.4um, Inj.:250°C, const. flow: 1.6mm/min He, Det.:MSD:280°C, FID: 320°C, Oven:50°C(1 min) - 40°C/min - 320°C (3.25 min)) 1H NMR (AV400, 400 MHZ, d3-acetonitrile): 6 (ppm) = 7.50 (s, l H), 7.48 (s, 1H), 5.03 (s, 2H, broad), 2.23 (s, 3 H).
‘NO‘ 2015/067647 - 196 — Preparation of the 2-chloroethyl-4—heptafluoroisopropylaniline starting material The 2-c1110ro—6-ethyl—4-heptafluoroisopropylaniline ng material of the structure (D—lb) has not yet been described in the literature. It can be prepared by means of known chlorinating methods from 2-ethyl-4—heptafluor0isopropylaniline, which is known from literature (e. g. /198399).
D—lb 4.9 g (16.9 mmol) of 2-ethylheptafluoroisopropylaniline (prepared according to US2002/198399) were initially charged in 100 ml of chloroform, the mixture was heated to 45-50°C, and then 2.18 ml (26.7 mmol) of sulphuryl chloride, dissolved in 400 m1 of chloroform, were slowly added dropwise. The mixture was stirred at 50°C overnight, then a fiarther 0.34 ml (4.2 rnmol) of sulphuryl chloride dissolved in 2 ml of chloroform was added dropwise and the mixture was stirred at 50°C for a further 3 hours. Thereafter, the mixture was cooled and the solvent was drawn off on a rotary evaporator under reduced pressure. The residue was taken up in dichloromethane, washed first with sodium hydrogensulphite and then with dilute sodium hydroxide solution, and dried with sodium sulphate, and the solvent was distilled off on a rotary evaporator under reduced pressure. For purification, chromatography was effected using a cartridge containing 120 g of silica gel with a nt proceeding from pure exane to 90: 10 cyciohexane/ethyl acetate (v/v). 4.25 g of 2-chloro- 6-ethyl—4—heptafluoroisopropylaniline were obtained.
HPLC-MSa): logP = 4.67, mass (m/z) = 324 [M+H]+. 1H NMR , 400 MHZ, dg—acetonitrile): 8 (ppm) = 7.84 (s, 1 H), 7.82 (s, 1H), .56 (s, 2H, broad), 2.37 (q, I = 7.6 Hz, 2 H), 1.06 (t, J = 7.6 Hz, 3 H).
Preparation of the Z-bromomethyl—4-heptafluor0isopropylaniline starting al id="p-644" id="p-644" id="p-644" id="p-644" id="p-644" id="p-644"
[644] The 2-bromo—6-methyl—4-heptafluoroisopropylaniline starting material of the structure (D-lc) has not yet been described in literature. It can be prepared by means of known ating s (e.g. EP2319830, p. 327) from 2—methylheptafluoroisopropylaniline, which is known from literature (e.g. US2004/92762). ‘ — 19.7 - D-lc 3.4 g (12.356 mmol) of 2-methy1—4-heptafluoroisopropylaniline were dissolved in 27 m1 of dimethylformamide, then 2.44 g (13.6 mmol) of N—bromosuccinimide were added and the mixture was stirred at 60°C for 1 hour. The mixture was cooled, d with water and extracted three times with ml each time of n—hexane. The combined organic phases were washed with water, dried with sodium sulphate and concentrated on a rotary evaporator under reduced re. Chromatography using a 120 g cartridge containing silica gel with a gradient beginning with pure cyclohexane to 90:10 cyclohexane/ethyl acetate (v/V) gave 2.44 g of 2-brom0—6—ethylheptafluoroisopropylaniline.
HPLC-MS"): logP = 4.38, mass (m/z) = 354 [M+H]+. 1H NMR (AV400, 400 MHZ, tonitrile): 5 (ppm) = 7.51 (s, 1 H), 7.23 (s, 1H), 4.86 (s, 2H, , 2.23 (s, 3 H).
Preparation of the starting compound 2—(3,5—dichlor0hydrazin0phenyl)—1.1,1.3.3,3- hexafluoropropan—Z-ol F NCS, F F\/ F AcOH F H0 0‘ \ _> HO F 0 F, F NH2 F F \NH2 To a solution of 2—(4—aminophenyl)-1,l,1,3,3,3-hexafluoropropanol (2.50 g, 9.64 mmol) (preparation, for e, W. A. Sheppard, J. Am. Chem. Soc. 1965, 87, 2410—2420) in glacial acetic acid (40 ml) was added, at RT, N-chlorosuccinimide (2.71 g, 20.2 mmol). The mixture was stirred at 75°C for 3 h and then at RT for 14 h. Subsequently, the mixture was added to water and extracted with EtOAc. The organic phase was washed with water and saturated s NaHCO3 solution and dried over ium sulphate. After solvent had been removed, the residue was taken up in MTBE and the solids were filtered off. The filtrate was concentrated under reduced pressure and the crude product was purified by means of column chromatography on SiOz (n-hexane/EtOAc gradient). 2.89 g (91%) of 2—(4— amino—3 ,5 —dichlorphenyl)—1 ,l,1,3 ,3 ,3 —hexafluoropropan—2-ol were obtained.
HPLC-MSa): logP = 3.04, mass (m/z) = 328 [M+H]+. 1H NMR (400 MHZ, d3-acetonitri1e): 5 = 5.13 (br s, 2 H), 6.02 (br s, 1 H), 7.51 (s, 2 H). ‘ - 198 — NaNOZ, SnCIZ.
F Ff, F F.,\.=F ACOH, H2804, HCI HO,X Cl HO .\ » — 4 a» F \ ‘~\ \ PK" \\\ r." )2.
/ L\f¢ \NH F NHz CI NH2 To a solution, heated to 55°C, of 2—(4—amino-3,5-dichlorphenyl)-1,1,l,3,3,3-hexafluoro-propan— 2-01 (1.88 g, 5.73 mmol) in 5 ml of glacial acetic acid was added dropwise a solution of sodium nitrite (455 mg, 6.59 mmol) in 2.5 ml of sulphuric acid, and the mixture was stirred at this temperature for a further hour. uently, the mixture was cooled to 0°C and a solution of ) chloride (3.37 g, 17.7 mmol) in come. HCl (10 ml) was added dropwise. The mixture was stirred at 0°C for a further hour, then added to ice, alkalized with sodium hydroxide solution and extracted with EtOAc. The organic phase was washed with saturated sodium de solution and dried over magnesium sulphate, and the solvent was removed under reduced pressure. 1.41 g (90% pure, 64% of theory) of 2—(3,5—dichloro—4- hydrazinophenyl)-l ,1 , 1 ,3 ,3 ,3 -hexafluoropropan—2-ol were obtained.
HPLC-MS"): logP = 1.92, mass (m/z) = 343 [M+H]+. 1H NMR (600 MHz, d3-acetonitrile): 5 = 4.14 (br s, 2 H), 5.90 (br s, l H), 6.50 (br s, 1 H), 7.58 (s, 2 H).
Examples I—T46-1 10 g (34.6 mmol) of 2,6-Dimethyl—4—[l,2,2,2-tetrafluoro-l-(trifluoromethyl)ethyl]aniline were initially charged in 60 ml of glacial acetic acid, and 5.02 g (38.04 mmol) of 2,6-dimethoxy- tetrahydrofuran were added. The resultant on was heated at 120°C for two hours. Subsequently, it was cooled a little and the volatile tuents were evaporated off on a rotary evaporator under reduced pressure. The residue was stirred with water and the solids were filtered off with suction. The ake was then dissolved in dichloromethane, and the solution was dried with sodium sulphate and trated on a rotary evaporator under reduced pressure. 10.38 g of l-[2,6-dimethyl[l,2,2,2- tetrafluoro-l —(trifluoromethyl)ethyl]pheny1]pyrrole were obtained.
V40 2015/067647 — 199 — F F F /F Fx-IF \ ..F \ \ /\ /F .\ .-'\ \ ’ \/ | 1‘F 4 5C | F __. F / I / 1.5 g (4.293 mmol) 1-[2,6~dimethyl-4—[1,2,2,2-tetrafluoro-l-(trifluoromethyl)ethyl]phenyl]- pyrrole were dissolved in 60 ml of n—hexane, and 966 mg (4.3 mmol) of N—iodosuccinimide were added.
Subsequently, the e was allowed to come to room ature and stirred at room temperature for 6 days. Then a further 242 mg (1.1 mmol) of N—iodosuccinimide were added and the e was stirred at room temperature overnight. Subsequently, excess aqueous sodium en-sulphite solution and a little ethyl acetate were added. The organic phase was removed and first washed twice with aqueous sodium hydrogensulphite solution, then with saturated sodium chloride solution, dried with sodium sulphate and concentrated. For purification, chromatography was effected using a cartridge containing 120 g of silica gel and a gradient proceeding from pure exane to 95:5 cyclohexane/ethyl acetate (WV). 453 mg of a mixture of 80% l—[2,6-dimethyl[1,2,2,2-tetrafluoro-l- (trifluoromethyl)ethyl]phenyl]iodopyrrole and 16% 1-[2,6-dimethyl—4—[1,2,2,2-tetrafluoro (trifluoromethyl)ethyl]phenyl]iodopyrrole were obtained. 998 mg (1.696 mmol) of a mixture of 80% 1-[2,6-dimethyl[1,2,2,2-tetrafluoro-1— (trifluoromethyl)ethy1]phenyl]iodopyrrole and 16% -dimethyl—4-[l,2,2,2-tetrafluoro—1- oromethyl)ethyl]phenyl]-2—iodopyrrole and 364 mg (1.7 mmol) of 4-chloro(methoxycarbonyl )phenylboronic acid were initially charged in 10 ml of 2-propanol. Thereafter, the air was displaced by argon, and 5.2 ml of 1 molar aqueous sodium hydrogencarbonate solution and 98 mg (0.085 mmol) of tetrakis(triphenylphosphine)palladium(0) added were added under argon. Subsequently, the mixture was heated to reflux for 3 hours. For workup, the mixture was cooled a little, then trated on a rotary evaporator under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic phase was removed, washed with saturated sodium chloride solution and concentrated on a rotary evaporator under reduced pressure. 1.57 g of crude methyl 2-chloro—5-[1-[2,6— dimethyl—4—[1,2,2,2-tetrafluoro(trifluoromethyl)ethyl]phenyl]pyrrolyl]benzoate were obtained.
\NO 2015/067647 — 200 ~ F/\ 1 .Cl \ F7/ FA A/-__,0I R _,,;m.,z R ,, \ l " T} O 1 OH F \ + F\ \ . \ —-* \ F / LI—OH F / N \ N \ f F o F \_ __ O 416 mg (0.33 mmol, about 40% pure) of crude methyl ro[1—[2,6—dimethyl—4-[1,2,2,2— tetrafluoro-l-(trifluoromethyl)ethyl]phenyl]pyrrol-3 -yl]benzoate are initially charged in a e of 18 ml of dioxane and 6 ml of water, and 61 mg (1.46 mmol) of lithium ide hydrate are added. The mixture was stirred at room temperature until dissolution was complete, then heated under reflux for 2 hours. The mixture was then concentrated on a rotary evaporator under d pressure, and the residue was admixed with a little water and adjusted to pH 1 with concentrated hydrochloric acid. The mixture was then extracted twice with ethyl e, and the combined extracts were washed with saturated sodium chloride solution, dried with sodium sulphate and concentrated. As residue, there remained 207 mg of crude 2-chloro[1-[2,6—dimethy1—4-[1,2,2,2-tetrafluoro(trifluoromethyl)ethyl]pheny1]pyrrol- 3-yl]-benzoic acid. 137 mg (0.11 mmol, purity about 38%) of crude 2-chloro-5—[1-[2,6-dimethyl[1,2,2,2- tetrafluoro—l-(trifluoromethyl)ethyl]phenyl]pyrrolyl]benzoic acid were dissolved in 15 ml of toluene, and 230 mg (1.93 mmol) of thionyl chloride were added. The mixture was heated to reflux for 3 hours.
Thereafter, all the volatile components were drawn off on a rotary evaporator under reduced pressure.
The residue was taken up in 4 ml of romethane and added dropwise to a mixture of 82 mg (0.69 mmol) of 1—cyanocyclopropylamine hydrochloride and 98 mg (0.96 mmol) of triethylamine in 2 ml of dichloromethane at 0°C. uently, the mixture was stirred at room temperature overnight. For workup, the e was washed with 5% aqueous sodium dihydrogenphosphate solution, then with saturated sodium chloride solution, and the organic phase was dried with sodium sulphate and concentrated. The residue was chromatographed using a cartridge containing 15 g of silica gel and 85:15 cyclohexane/ethyl acetate (v/v). The fractions containing the product were concentrated and d by means of preparative HPLC (Zorbax Eclipse Plus C18 1.8 pm, mm in a gradient in acetonitrile/O.1% aqueous H3PO4. 13 mg of 2-chloro-N—cyclopr0pyl[1-[2,6-dimethy1—4-[1,2,2,2— tetrafluoro—l—(trifluoromethy1)ethyl]phenyl]pyrrol-3 -y1]benzamide (compound I—T46-1) were obtained.
HPLC-MS": logP = 4.90, mass (m/z) = 558 [M+H]+. 1H NMR (400 MHz, tonitrile): 6 = 7.63—7.67 (m, 2 H), 7.56 (s (broad), 1 H (N—H)), 7.51 (s, 2H), 7.41 (d, J=8.3 Hz, 1 H), 7.16-7.17 (m, 1 H), 6.75-6.77 (m, 1 H), 6.72-6.73 (m, 1 H), 2.14 (s, 6H), 1.55- 1.59 (m, 2 H), 1.32-1.39 (m, 2 H).
VVO 2015/067647 398583? anosfioaf NBA m"gall-Ea OHBdemewaNm £90 mus—NH. NH- 07L nU TIL .3 AU p/ H/ - - .LU.‘ 802 3:: HH vmm Rm 9mm wow moo mmo va bum amus— «Hm 5% NV 0% 9H" HHV Him Tm WV NH" 0% ban WV m4" 0% HIV HIV 1389298 398a HbHHo HbHoEoHoho A2580- -N"NAN0-NN #303298 53350- 39052328050- 89380- 1389298 H oHoxnoAHbHHoaoHoEHEV -AonflamHhfiH000003mEH H H H %%:§ HH HH i m0 Illfififil a :3" El HrH «Sm E m HIJI mm m$0.0 m$0.0 erH0-0 £06 £06 £06 §Im £06 £06 £06 £06 m$0.0 o hmm0+0 €0-06 £6-06 $10.6 $10.6 €0-06 €0-06 €0-06 F"Hm0.H.0 £00-06 m$0.0 m$0.0 mHLH0.0 £06 £06 £06 £06 £06 £06 £06 £06 £06 £06 £06 .02 o H N m o h H- N- m- v- m- 0. m- H- .NW BL mHH mHH mrHLH MrHLH ©-mrHHH BL w-mH-H MPH H-mrHL-H H-mH-H H-mrHL-H H-mrHL-H vH-mrHL-H mHLmrHHH H-mrHL-H mrHLA '03J >- PAL3HEP 2U 1 4/47.3_./ (2 Q as; FE: 2? mom Sum com m5 com Nmo mmo Taoaofiohoflodgmov- EmoEoHozvoqfimoY 358335 E 1389298 98 H H anoséquv-H Emoumofiohofloqgové :- H" m EH m E m m m a. H! 0 5 m6 $5 . m- $5- O 5 5 N4 m5 E55 m5 D Hm E E : fix" m E m Elfilfi mm mmo- 5-5 O m$0.0 $6-5 $6-5 $6-5 $6-5 $6-5 $6-5 "ma-TO Ema-#0 WHO-O $6+5 $6-5 $6-5 $6-5 $6-5 fig-TO Hm m$5.5 m$5.5 m$5.5 m$5.5 55 M55 M55 m$5.5 m$5.5 m$5.5 m$5.5 5-D 5-5 5-5 $55-5 $55-5 $55-5 i ‘ .oZ m m ON- Hm- MUN-MBA mm- vm- mm- om- 5N- wN- mm- om- mm- mm- mm- m mm. m- .Nm Tm-flé Ta; mHA mm; MFA m-HA mH-A "EL-H mHA MBA mHA m-HA 3; why-H mHA who-AHA "PH-H 2% mu; 2 nl\ 3&2 3:: :3 0mm .mmm Em com mum 9m. Wm 5% 0% 9v 06 NM NM fim fim man m...» film WV iv 0v 5v II...-Emoaofiokoflofiwmov- @8333 a-m-qsoé H anosEofifiv-H amoaoEvoafia-H EQOHQOMohvongov-H anoiofloam3: m E m i o o I_E_ BEE. -m- m- 6- 6- 5- o o U E ' 5 33m m m m Wfi-wm Elm Em m DIE—Em m E E -D £55 £55 $5 $5 55 hmmU-H-O $6-5 $6-5 $55 $55 $10-.
To $6-5 mEND-O mEND-O WES-O mEND-O m-U $5 $5 $55 $55 $55 $55 $55 $55 $55 .oZ wm- om- ow- 2m- NV- mv- 0v- Eu- ww- av- om- Hm- mm- mm- wm- mm- om- hm- wm- .xm m-H-H mH-H mH-H mH-H mH-H mH-H vv-mH-H mw-mH-H m-H-H mH-H mH-H mH-H mH-H mH-H mH-H mH-H mH-H mH-H mH-H mH-H mH-H "H5-I PCT/i2?,,201 AWL" "1,,"-\r b N: 9.12 H.m Wm can QM 3 NH" 3 0...» we 9v min m4" m4" 9v 0w H4" NHV Hugo- im Nm m.m NH" min 0% 9v II"!0HanoHQoHoonoquov-H Tao-$298 HbHoEoHoho HbHoEoHoho HhmoaoHoxo 3%on meohmoHohofloqgoV- HkaoaoHoxnvokamoV- me£0§2988§8¥ Ego-3298 £30329? HbHoaoHokmvoEwhov- HNAAHOEOHQAO Hokmvoqgov- HaoaoHQAo 3905298 Aonwkmov- 3903298 memoEoHQAOAothov- Ego-£9298 H%monHoHo\nvonm>ov- Tao-:83? HEBAHOHokvoqSGY 3989293 35-5525 H H H H H H H H H H HMH E E E O ElO O II O HH-O EAV "r": 3 HIHI 00 D m< H0-0 5-0 mm. 4 £5 m- 0 00 o EAV .4 5;; £5 aw- m- OD 0 H-H-U azm HE EEE‘IEE mm E EM— SEE mIHH ££ E mm mm $5 nH-O a.) HOO HH-O O MED-O «.m— WHO-U $6.55 $6-5 $6-5 "ma-TO $10-70 $6-5 $6-5 $6-5 $6.55 $6.55 $6.55 $65 $65 $65 _ _ 5.0 $55 "5 nH-O Emu-U mHAD-U mHHD-O $10-0 MED-U mmNUO WES-O WIND-O mflwod mH-HNO-O £65 £65 £65 £65 £65 £65 £65 £65 £65 62 mm- 00. Ho- No- mw- Huc- mo- oo- Nb- mo- mo- on- Hm- Nb- mm- Huh- mn- hm- on- .MM mH-H m-H-H BL mH-H m-HHH mHH 2-H mHH now-TH m-HHH m-HHH mH-H MBA mHH m-H-H "Bu-H m-H-H £1-th mHH mem-HHH m-H-H --H -H NwLm-HHH mw-mH-H 33¢ 3:; :2 0% WWW 8m 2m 9% EV 9% 9% its 3 3 E. 3 v m am in 3 3050 A oboo . oé 98 3535293 0-022020 o s. as. 3080205 308835 #380298 383205 0 o anoéofiofifii AOQSGYH m m 0 H E Hi w: m0 m0 m0 00- m I0_ Hflifiz00- m -0 #0- 0 0 £0 0 m0 4 0filmm zflmm0 Em A m0 m - m- Em m m m Sm m m m 0_ll0 m$0.0 00- m$0.0 mmofiv £0- mm £00 €0-00 bmmOA.O - Hm 00.0 mm0-0 MED-O - E .ozam mw-m-S m3: mi: 8&5 ha- mH-H wm-ME ooH-mH-H 83.5 my," —/ PC1710!) 7,014/(173795 $02 3:: :0" 00m 0wm M00 :0 0%m %bm mg 000 MS %M0 %mm m%0 00m. mmm 0Mm 50% m00 mwm :0 . 0% 0% m% 0% N% 0% %% 0% 0% 0% WM M.% WM 0M 0M 0M. m% 0.M 0M WM wM 038020539030; anofiaoflofié; Ego 0303298 300320530050- 0303298 0305293 2 2 3005298809802! I0Hi 'Hm mm0 E I E m0 mo I 00- 0. -000’: I m‘nl 0 0 4 7. 7. ZIZ Z Z E 0.0 0.0 m. $- m. 0 0 0 I .Em m m U: m E Em m H E Iflll M000 m$0.0 m$0.0 #10- $00.20 hmmmol.
T0 TO mnH0-0 m$0.0 m$0.0 20-0 m"20-0 mHMO-0 .OZ S 2 2 2 2 .Km 8va 020 835 83: 83: 235 :35 E: 235 :35 ES 33.5 3: 00 35 ONE: 83: 02a: -0 %NTMH-H mNH-MHA AL AU 00 PCT/EPZGH/OHWS mg: 3:: Eu mmo mm? mow owv moo mg #3. mom mwm 30 00m com :0 gm. Sm Wm Wm 9N Wm 04m QN 5m 3" Ow Wm Tm Eu I'll!" EIIIIE EIII-o $089298 Tao-$293 T389298 335298 Ego-EOE? E E m O ' I him - m «:M - m m m IIIIIHII m mm 00.0 $0-0 $0-0 $0-0 $0-0 H0-0 $0-0 $0-0 $0-0 $0-0 $0-0 0-0 mm hnHm0-H-0 $0-0 $0-0 $0-0 $m0+0 $m0+0 $0-0 $m0+0 $64-0 $0.00 #1040 $10.00 $104-0 $0-0 0-0 00.0 0.0 $0-0 $0-0 00.0 0-0 $0-0 0-0 0-0 $0-0 $0-0 .02 0N .MH ONH-mH-H TmH-H mNTmH-H mNH-mH-H omH-mH-H HmH-mH-H NmH-mH-H H-H VmH-mH-H mmH-mH-H omH-mF-H hmH-mH-H me-mH-H 20C) — PCT/EPILGM/{WF-WS m2": 3:; :2 3m 2% 0mm mmm 7mm 3% mom 2m m3" Nmo oom mwv com Han NV TV 0% 9v van Wm Wm 0% WV Wm 9m of fihmohmofiohofloquov- <38"??? Ego-$298 333293 H HhmohmofiohoAOQQAOV-H O ll In. 0 we -0 mE00 a 2 Z EHE3 In 00-0 hmm0-fi-0 £0.0 m"6-0 mnH0-0 m$0.0 m$0.0 m$0.0 mMAO-0 m$0.0 m$0.0 00-0 00-0 5-0 .Nm mmH-mH-H oE-m-H-H :l-mH-H -H mE-mH-H gay; #35 $25 $22 $35 $33 335 RES ) 10— Tu1. C"f/EPZUM/W § 795 mm": 3:: :0" 2% v8 to 9% 0% woo m3 $0 Aims E m2 3 M2"- 3 mam 3" 2" 8 Eamoéoflongov-H anosfioaéi anoio 0380203 -anoEmQ-Hmoofia- T303298 #380203 H anogoflofiév-J E m mm m<0 I... mm0 l.- Ed m0 £ 00- 00- 5- 0 0 00-0 O S m0 E m0 -0 E0: m0 m- Em mllm m m m m EH- gag Sm m m m m m E m 2 5.0 z z 5.0 $0 00- mm £6-00 £0.00 $104-0 €0-00 €0-00 00 $10.00 €0-00 m m Hm 00-0 -0 mm -0 63% m00.0 m N -0 66% mm -0 N030m E "HO-O m00-0 m000-0 573$ ND-m: «20 $3: 52-2; $35 mmfléHA SEE .835 —211- PCT/EP2914/G73795 an: 5:: A_A« me bum mmm com Now mmo How EH. film 5% N4" 5% of g Tm Inn-E‘Efll-I -QNEBSBOSGEV 3989298 -Nnmé H.0H- Néa- éfi 350-8% $305293 IO o IO 0 m £0- IO 0 IIHLHOllEIO m £6- IO mIO MED- m EIO D mm0-0 MBA H «m .oZ H- N- m- 5. oENH 95 .Nm— mHIH mHA mung WE: 92L EL j - TMPZO‘M/fl7G47. :/ fl} mm"; 5:.— :2 3m 2m gm Nmm \Ibm me mmm mmm I|| 3m Em mom mfim mmm com mmm mmm wbm 313 VIN prev N4" m4" ban Ow WV m4» WV I1" 5.? WV Wm 5m 2V N-v 0v ITA Iofiokmofiouahov- fl H . .
OH OH 0 0 0353quon Te. E89203 3.8. 3.0-: Tao-I. E2920? .8. .OH. HIV-OI: I H Iofioxmofloqgové voamImoVIH I Hm I E I m _Hm .3 40 0 I Ilal allllll O I!"EnIEIIIIEflEI mIU E. m- III-0 I laIIII O 0 EIO I- I-fl-III-0 HIE"a-m- m- I0- I0- 0 .0 0 0 0 I0 Ed m- I DalH0_I0-0H III-Elm0 ID 7% II- I0 I I IO zIHO :0 m MEUIOV m$0.0 I20-0 £0- I. m £0- m InIIIIfiII 0 IE I 0 EEIIE I EIO m0 m0 -’m-0m- m- m- I I 0 IO .0IE III 0 0 II b b"HMOIIIO‘ IIII0-I-0_ ImI0-I-0 ImI0- 5 h I b m m m m H I- III IT . III #10-- II T O ImI0-I-0 ImI0-I-0. 0 D IIIm EIO SID EIO a IO m0 mIO EIO 0 m$0.0 mEUIO mm0-0 m$0.0 I$0.0 mE00 I$0.0 m:00 .oZ m .Mmm mImHIH 3-2L :Im-HIH NEE MEI-E III-m5 WEE Sim: 2&5 Ia: 2a: 8-2: IE: N35 m3: IIN-mE ENE FE; 2? 05 0% 034 win :um com ovm Nwm com m5 vmm cum com mum coo 3.2 3 SN 3. Wm mm 3. 3 3 3 3 in om 3V 3 3 3 3 Wm we. -29mofloquov- E-m -298 £38 Hmonono Tao-HQ T305298 T303228 -oEo%voq§ov-E #- Tm. E OH oH 0 T305293 mnH0~E0 mm0~E0NE0 o-H. m"E0NE0 m-HHfioHHt A2580; <3on . T303298 E oHHwHAoV-E H ""11".HHHHMH:5..55 HHH HH H E E :H IIIHH Ea OHIIIIWO Ia E-0 HHH a-In E-0 HHH III .0 E00 E0-0 H.
HHIIIHHHHIlia» m6 E-0 E0 E-0 IIIII HHH m6 E-0 E0 E-0 m E IHHTH? SHE m E E :HIIHIIIIII En‘lfi Hmod HIIIIIHH E-0 E-0 HHH II IIII mo E-0 HH- E0.
H- mo $6-.
H- H 0 0 Ham-H6 #104-0 TEM0-H-0 HmHoHo— hr-Em0-H-0 H mo E-0 mo E-0 E-0 mo E-0 mE0. mE0-0 mE0-0 mE0-0 E00 E00 5.0 mEN0- I 0 $00.0 m"H000 mm0O-0 m,E0O-0 mEm0-0 E00 0 H .2 8-2; 0N- hm- wN- mm- om- Hm- mm- mm- vm- m w m- om- hm- mm- ow- $- NV- mv- HQ mH-H m-fl-E mH-H mH-H mH-E mH-E mH-H mH-E mH-H mH-E mH-H mH-H m-mH-E mH-E mH-H mH-E mH-H mug-E $32 3:; 2?. 0mm mum 0mm film new wmv m5» #3 9v o.m NM N-m fim fim man WV #6 mew .3" m4" 0% fim NM 0% Qm . m"EUNE0 -oEo>vo:m%oV-E 3.8. -oHo\mvonm%oV-E O -§% 3.8. £38333 E50. $5.: -29mofloqgov- TAQOH. £096 3.0-: 3.0m. gai- E -oEo~mvodm%ov-E HE E E m >9 O InIna 07 .4 - E. 0 -0 -0 m0 E0-0 0 3- E0- £0- E0- E0- 0 IE 0 0 5 0 EEE EE m- E- E ~< -0 - - - - 0 IIEIIIIII 0 m0 0 i E0 m- E - m0 E. m- -0 -0 0 -0 0 0 0 m _m E0 a- - -0 0 0.0 -O 0 ‘mE000 III - 3- -0 - m0 E- E. 0 0 3 B b m m 0 £0-00 m0- - - - £0-00 mo -.- . L- - - 0 0 E0 m0 £00 £00 £00 £00 £00 £00 £00 £00 000 m0 m0 .oZ in- mw- 0v- Du- wv- 9m- om- Em- Nm- mm-mH-E fim- mm- wm- 0m- wm- mm- $- mo- .NE mH-E mH-E mH-E mH-E mH-H mH-H mH-E mH-E mH-H m-H-H mH-E mH-E mH-E mH-E mH-E 03: mH-E mH-E WHO 20} 5/0 6 7 61-" F/ an: 3:: :2 V?- mum \o v—( (\l 0 m to mmm wOV OVm Rm" V.V NV mV ©.V V.V w-V WV b-V WV 0V m.V WV 5V V-m V.m Wm m.m NV m.V o.V Inn-E111!" T??? -oE0%0A0$§ov-E - E -298 E E .OH. .89 55555 138336 03589880; V». E. . 8. $380203 03538300- 8. 03338980- M OH - AoSWNAOV-E 90$. O$§0Y .05 IOHONAOAOHHNKAOVIH 3.8. Ego-@298 E E E - EEE'IE I'i E m E afllfifll 0 m0 E- -0 -0 E0 0 E0-0 $0 E- 0 HEIIE0-0MOIO - E0-0 $0 HIM—"IO E. E- 0 $0 IIEIII5- 0 0 mo-0 E HIH EHEEIIH $ 5 E m I:H 5 $0- m m E0- mo E0- E0 - 0 IEIIIII'I 0 0 0 mE00 :55 ml m - 5-0 -5 E0 E0 0 $650 $650 $650 $650 $650 $650 $650 $650 l-EEEHIIHEE:55 $650 $650 $650 $60 ~$ $0 $0 $0 $0 $0 $0 $0 $0 a $0 $0 $0 $0 $0 $0 H$ $0-0 $0-0 $0-0 $6-0 $0-0 $6-0 $6-0 $6-0 $6-0 $00 $6-0 $6-0 $60 $6-0 $6-0 $6-0 $6-0 $6-0 $60 .oz mo- ow- $- mo- @- 05- :- Nb- 55$ 8-2: Vo-mH-E mH-E mH-E mH-E m-fl-E mH-E mH-E mH-E mH-E m3: E-m: 3m: 052$ 5:: gm: 3.2; ow-m: $3: mw-m: n/_ 11 6 $53 3:; HHHH 0% 08 HHS mom mm 0% o?- mmm wwm N8 E a? 9% EH 0. 3 3 o cm o m SH 3 . x H m HH. . . m m m m . Hm 2_éHaH-< HH m mHH0HHH0 HHH-m-HHHHHDHHHH H3830? -oHo§oHHHH§-H H H H .8. H3830? H388?o HbHoHHHoHozo- HHHHHHHH.HH-HH0 H -203?an M .8. cOH. OOH. .8. :20 533%: 3.8. HEoHHHoHaHo HbHoHHHoHQQ HHHHHo-HHHHOHOHHo E '5 HH H m HH aEH 0 0 0 HH- HH- m- 0 HH-0 0 -0 IafiIna-0 0 m0 .35.-0 InaE35Hi H0- H0- £0- H0- H0- H0- - H0- H0- H0- H0- 0 0 0 Inga 0 0 0 -H 0 0 0 HH- HH- m- 0.0 m0 m- z z -0 0 0 0 0 HH- m- HH- m- HH- HH- HH- 0 0 Em 0 0 0 m0 0 -0 -O Ham HH Ham HIIIHHO-0 IfifilmI"figla m zfllwH m m m mm £0- Hm. H0- H0- H0- 0 0 -0 £0- 0 0 6.0 0 0 Hm m- m0 m0 m0- HH-0 - mi HH- HH- 0 0 $0 HHS-H0 HHHH0-H-0 mHH00 m-H0o-0 H mm WmH0-0 $0-. H-THH0-.
- - H- H- 0 $00-0 Hmm0-H-0 HnHm0-H-0 0 0 m0 m0 m Hm - HH-0 - 0 HH-0 m0 HH-0 m0 Hm mHHHH0-0 m"H00 mH-H0.0 H0 - - - 0 H0-0 H00 H0-0 H0-0 m00.0 .oz a g - - - - .me MAW-m: Hum-m: 3-2; E - - - - H Maw-m: 03: Hie-H H HHm-mH-H wa-me-H a-E-H OOH-m5 _ HH - WHO '20], x1/067647 PCT/f4'PZ(I],4/G73795 £2 3:: A:: 30 9% 9% mom1 3m 3m 3m Ham ANAHI- 3 . . . 3 g. 3 3. . g. 3 w.m 9m 3 Moo-H. Hé. H3886? To: 3080203. fi.OH- 5356930; 13on HQOH. >989 Hé. 3080203 3080203 -oHomQAoHHaoV-H.OH. 3 I £0 H m £0 a 0 IaIIIIIIII0LIE 0 0 3 V4 m0 - E0 m0 m0 -0E.z H0- H0- 0 0 60 E552 £0- H4IEH m0 m0 InI'IIIInllllEEZ Ifi0ll m0 _m- I0 -0 0 DHMm Eli.
NHMm - m m m 6.0 £0- £0- £0- £0- 0 0 mm0-0 0 0 m:0-0 Ella m0 m- ID 0 m0 m0 E s EE0IHmH0-H-0_E m0 HmH0-H-0 I I $10-.
I _HHHH0-H-0 H- I H-rHH0-H-0 :H-IHH0-H-0_ HHHH0-H-0 HmH0-H-0 Nm m0 I m0 I m0- I m0 m0 m0 Hm H00 I m00.0 £00 - I I M000 M000 m00.0 m$0.0 «oz .- I I .xm—H SEE I 83: 33: :3:- - I - I :3: wHH-E-H :HHLm-S ONE: PCT/EPZOI4/0737 f5 :2 woo 3 m3 @0- wmo vow 3m wwm o Rm" 3- 2V 2 m.N ago. a 3- m . . .
N 3 v . 0-23 5338350; T300. 3.0.: -ofiokmvoqwhov 3.8. -BQGAOQSGYH 3.8. 0320203 0389203 Ego-E298 EHEHEHIE £0 InIIIIIIIIInna"mafia£0 £0 anEafiEH.m B 0 0 .0m0 im0im0-0 E -O Ed m$0.0 50 £0- 00-0 0 0 $0 m0 nzm £2 «:M 20 lfilm m llm$0.0 H0- - 0 m0 ia. m0 _m-0 m0 m0 m0-O m HO -- EEI -- €0-00 £0- - 0 €0-00 O €0-00 $104-3 «Ma H3 00- m0 m0 m0 m - m0 - U m0 m0 Hm m8 £00- 00-0 00-0 00-0 5 n m00-0 £06 - 0 00-0 m00-0 5-0 .oZ N2 - - - .xmm 8;: ONE: wS-mi 020 SHAH-H 2- - RES I - H mfl-ME $35 mam-mm; -219— mmflfia Si 2H 0mm com woo «Ne H0012 H14 n w - mm. . . m m _%IEE -oHonvoquov; H - . a- m .8. -ofiokofloqgov- .OH . -ofioxofloamhoV E50: H -OEOGHHEOE <3on fl E aIEEaEl-E. 0. E3 a.0 o Ed 00 laE :6 m- -H4.o flood 5-0 H0- 5-0 5 0 o IEIEE-IEE-lflm alll0 - EEIII H0 :6 m6 0.0 EIIEEIIEIIIIIIII m6 m m m m m m mmo- z O 05-0 H0 a-fi m -o II Ed H0 mo - 0m $104-0 £6-40 Mmoo- #10.- o 0 H- H 0 0 Hm 3.0 m6 H0 EU- H0 m6 m6 Hm mEUO fled H0 0 £00 #0onM - .25 0.3-2.; HHHH-mHS a: - - - BL- $35 E35 A}; A} n!\ PCT/EPZ01E4/073795 was; 3:: :9 who mom mmm mmm woo mmo 0woo vmo 9% cow who mum Nam mm? 02m mmm owe . :0 5v Wm Qm Wm- 0% o.m 0% m4» fim m6 WV 0% m.m NM 5m WV 2 . 629889980; -298 H -298 QB . 0 OH <38 Thu-OH OH . 2930:8298 20305298 09895920000332 3989298 398898 29303298 390E298 629838980- Tm . . . - 20305298 A2580- 2 fia80-2 620832380; 33980-2 2 3.8. 2 E E 'E E -0 Balm- E IafiafifilRafi Ea E 00 EI0 Z lfi Hm-U aflaflfllll N02-0 00 E-0 0-0 IIIIII-IIIIIII 00 00 mm $102-0 £095 $102-0 £00-. £00-. £0- £0- £0- $10-. 0- 0- 0 0 0 H- o 0 0 mE000 mE00-0 20-0 .KE mmE-mH-E omE-mH-E me-mH-E me-mH-H mmE-mH-E 03-mH-H SEQ-E -E mwfi-mH-E vwfi-mH-E mS-mH-E ocE-mH-E hofi-mH-E wofi-mH-E moE-m-fl-E oS-mH-E :E-mH-E "’0 201 I:@67647 421- PUL/EPZGlaf/O73795 an: 3:; :2 com mmm moT 2% :o 02m Nmm 3m mmm mom Sum 5mm Now Sm mmv mmT mom c212 qm VT 24m WT YT 1m N.m o.m WM Wm o.m Tm QM 9m Om Om Tm ll-II'EHEImmIIEIIIIII T303298 T303298 I298A0998VIH T803. I298Aoq§8vé H.OH. T383298 T303298 T383298 I298 A0938; TnQOH. I298Aoq98VI2 T383 -030; H.0H. T88. I208Aon98Y Tm.8.
E m I m O O 0 EIO E. THUI m. 0 0 ID ID - 20- "HI5 O 20-0 0 o EIO m0ID E I Hull EUID aEIEEI E I0 m m I I HID a- I o EIEEIIE 33.0 E m- O ID D- IIEIIIII I $102-0 n .0 m m U mo o I . IHI 0 mmOIO .m mmmomo 6-0 6-0 £00 £90 .Nmm NSImHIH H TSIMHIH H whHImHIH PSImHIH wSImHIH 05-33 OWHImHIH $2-33 NwHImHIH meImHIH $3-33 meImHIH owHImHIH $2-33 meImHIH \VU S/G 641' '7 mm": N}:22. 3-n 3m So mg m: mg 03 3o So its m g m 0 E 0 . 3 . 3 :4 SEE . . .
. . . . N N v w v 3 E E .IIEIIIII -20HnvoquAoV-H -298 <8on E .8. 3.8. 5583500; T305298 .8. 33:63? 533: Efiofiakaem -oEo%vo§%ov-E EOE 898-3 EOE A9580- .8. <3on #.OH.
H -oEo>vo§%oV-H 5322300; E - a.0 B la OE 0 In E- - - E- E- 0 nfiaflfillfifl E0 mo mo Fe -0 0 0 -0E0 Ed ,4 - - E0- 6. 6. E0- E0- 0 0 5-0 0 0 0 0 60 3H E0 m. -0 E0 o E0- moI H< - E- m0 -0E0 -0mo o -0E0 E-0 m6 Em H m E a mE-m00m n70 - 5. o WWW Ila :- m-O m- -0 Ed 0 m6 I0mo Hm m0 0 Ham-Ho. $6-3; $6-5 llflfilfifillifil - I 0 aa mo mo mo Hm 0.00% - AN m mENOm-0 mmwomo £50 m-O Edmovm m £06 @180I H53 573% 03 3H SN SN - - - - I 96 2- - Ema-mH-E - M:- - E N25: 83: va-mH-E REE Mai-S 93a: oom-mH-E m:I E PCT/f"j \-J.7 (173795 852 FE: :2 owm com Hmo Ham omo 58 NH0 moo Hmo 08 wow Hmo 0N0 Hmo Nmo wmo 5mm- am- WV in WV HHN 5% man 5m H.m VA 2 IIIHIII Wm H Wm QM Haw -oHo>vo§%ov-H H».oh. HNEOHAHOHQS -298 A2530- #389 Ego-£298 3005298 -oH0%von§mov- Ego-H. HbHoEoHomo HbHokHoHokmo Aoq§mov- 3.8. 3980298 30009298 03330050 H.OH. HmmoEoHomo HNEOHAHOHQG H H H H fl la0mHH0 E $0 -- 00 0.0 .15a Z HH-0 H-H-0 H-H-0V m-O E.
H-H HH EEHEEIIIII-IEIIIIII H0- 00 a a- a H0-0 II- ['0' H0- 0 0 o 0 m0 m0 :0 m-0 _-H-H0m. H-H-0 0.0 bmm0-H-0 anm0-. 0 Q"HMO-H0 €0-00 €0-00 €0-00 b"Hm0-H-0 anm0-H-0 hnHm0-H-0 anm0-H-0 £0000 m0 Wm HH-0 HH-0 m0 m0 E0 m-0 m-0 H-H-0 E-0 HH-0 E0 .mH Z00 Z00 -0 £08;- mHHo0O-0 H-0 H-0 NnHH-H0O-0 NnHH-H0O-0 NnHHH0O-0 N"HH-H0O-0 #5000 mnH0O-0 H0-0 vow- WON- GONI NON-MFA wom- mom- o H .oZ Hm- HN- NHN-m-HHH 235 :35 235 £35 STE-H mam: 23: ONN- .me mH-H m-H-H MHHH mH-H mH-H m-HHH m-HHH m-HHH VVO 2015/0676-47 224 — PCT/EP2014-/073795 flag 3:; 2? mum mom NE 0: 9N5 9% 005 mmw v:- 2580 9% Adm" "28 o.m m.»- 54» NW 0% WV iv fim A: m Boa foam 50329350- :3on -29mvoESmoV- doom EH H H 0-H mNd . 1389298 .OH. + "Sagan 0 63580350; 18on IIEI H -29nofloqwhoV-H .8330 m< EEEEEEE RafiIIEII M m "< as EIIIIIII #855 3T WEE < H gm cm 56 m-H < 3-0 mmm £8 04g E: E-0 E 0.0 m m bBUo< "Ema-5 E m B235 6% H-0 H8300 B88 m-O l 955% $85 01ED $3 h"100 hmm0-H-0 $6-5 $6-5 $6-5 $6-5 08 "fits 00m mg .aa m-0 E-0 E-0 E-0 m-0 E0 685938 VHHDOO/w cow-mom 00-0 0-0 #0 ofiaosow m@00-0 m"H00 was 0-0 mm00-0 m(-40.0 m"H00 $335 0HUm 50825 HNN- NNN- mmm- VNN- m w Pa MN- omw- hNN- NN- mNN- mofldflom #:083me 303m mH-H mH-H MBA m-H-H mH-H mH-H mH-H m-H-H m-H-H 3 l.- as" Mae? "’0 2015/067647 GA 7. 2014/073795 0:00:00: >> wle.0 0.: v The peak list for one example therefore has the form of: 51 (intensityl); 62 sityz); ........ ; 5i (intensityi); ...... ; 5n (intensityn) The intensity of sharp signals correlates with the height of the signals in a printed e of an NMR spectrum in cm and shows the true ratios of the signal intensities. In the case of broad signals, several peaks or the middle of the signal and the relative ity thereof may be shown in comparison to the most intense signal in the spectrum.
For calibration of the chemical shift of the 1H NMR spectra we use tetramethylsilane and/or the chemical shift of the solvent, particularly in the case of spectra measured in DMSO. Therefore, the tetramethylsilane peak may but need not occur in NMR peak lists.
The lists of the 1H NMR peaks are similar to the conventional 1H NMR printouts and thus usually contain all peaks listed in conventional NMR retations.
In addition, like conventional 1H NMR printouts, they may show solvent signals, signals of stereoisomers of the target compounds, which se form part of the subj ect-matter of the invention, 2O and/or peaks of impurities.
In the reporting of compound signals in the delta range of solvents and/or water, our lists of 1H NMR peaks show the usual solvent peaks, for example peaks of DMSO in DMSO-D6 and the peak of water, which usually have a high intensity on average.
The peaks of stereoisomers of the target compounds and/or peaks of impurities usually have a lower intensity on average than the peaks of the target compounds (for example with a purity of > 90%).
Such stereoisomers and/or impurities may be typical of the particular preparation process. Their peaks can thus help in this case to identify uction of our preparation s with reference to "by— product fingerprints".
An expert calculating the peaks of the target compounds by known methods (MestreC, ACD simulation, but also with cally evaluated expected values) can, if required, isolate the peaks of the ‘ — 230 - PCTl/EP2014/07379Ln target compounds, optionally using additional intensity filters. This isolation would be similar to the relevant peak picking in conventional 1H NMR interpretation.
Further details of 1H NMR peak lists can be found in Research Disclosure se Number 564025.
Example l-T2-1: 1H-NMR (400.0 MHz. CDBCN): : 8.297 (5.2); 8.291 (5.1); 7.846 (9.6); 7.825 (3.3); 7.818 (2.0); 7.545 (3.5); 7.525 (2.9); 7.523 (2.8); 7.443 (9.1); 6.977 (1.2); 6.544 (5.1); 6.538 (4.9); 4.085 (0.4); 4.068 (1.3); 4.050 (1.4); 4.032 (0.5); 3.440 (0.4); 3.374 (0.4); 2.862 (0.8); 2.853 (1.2); 2.844 (1.9); 2.834 (1.8): 2.826 (1.3); 2.816 (0.9); 2.240 ; 2.150 (23.6): 2.086 (3.2); 1.972 (6.1); 1.965 (1.2); 1.958 (2.9); 1.953 (13.9); 1.947 ; 1.941 A32.9); 1.934 (22.7); 1.928 ; 1.436 (16.0); 1.269 (0.5); 1.221 (1.6); 1.204 (3.1); 1.186 (1.5); 0.790 (1.0); 0.778 (3.2); 0.773 (4.1); 0.760 (4.2); 0.755 (3.2); 0.743 (1.4); 0.614 (1.3); 0.604 (3.7); 0.597 (3.9); 0.593 (3.4); 0.588 (3.3); 0.575 (1.0); 0.000 (3.0) Example I-T2-2: ‘H-NMR (400.0 MHZ. CDSCN): 8: 8.311 (4.9); 8.304 (5.0); 7.898 (10.0); 7.878 (3.3); 7.872 (2.0); 7.824 (2.0); 7.583 (3.2); 7.561 (2.8); 7.444 (9.7); 6.555 (4.9); 8.549 (4.9); .447 (0.7); 4.088 (0.5); 4.088 (1.8); 4.050 (1.8); 4.032 (0.8); 2.240 (45.7); 2.146 (80.1); 2.114 (0.7); 2.108 (0.7); 2.102 (0.5); 1.972 (7.1); 1.984 (3.1); 1.958 (8.0); 1.953 (38.5); 1.948 (85.9); 1.940 (87.5); 1.934 (82.1); 1.928 (33.1); 1.775 (0.4); 1.789 (0.8); 1.783 (0.4); 1.591 (2.0); 1.578 (5.7); 1.589 (5.7); 1.558 (2.8); 1.518 (0.4); 1.437 (18.0); 1.410 (0.4); 1.369 (2.8); 1.356 (5.7); 1.349 (6.0); 1.334 (2.1); 1.298 (0.3); 1.289 (1.9); 1.222 (1.9); 1.204 (3.8); 1.188 (1.8); 0.000 (4.5) Example l-T3-1:1H-NMR (400.0 MHz. CD3CN): 8: 8.118 (11.7); 8.081 (12.8); 7.889 (7.9); 7.883 (8.8); 7.887 (0.7); 7.852 (4.9); 7.848 (3.5); 7.831 (5.5); 7.825 (4.3); 7.535 (18.0); 7.463 (7.8); 7.442 (8.2); 6.895 (2.5); 4.068 (0.8); 4.050 (0.8); 3.912 (0.7); 2.881 (0.5); 2.871 (1.5); 2.882 (2.1); 2.853 (3.2); 2.844 (3.2); 2.835 (2.2); 2.828 (1.5); 2.816 (0.5); 2.270 (0.5); 2.281 (0.3); 2.143 (107.9); 2.138 (145.5); 2.111 (71.2); 1.972 (5.1); 1.984 (10.3); 1.958 (27.0); 1.952 (94.0); 1.946 (180.4); 1.940 (199.1); 1.934 (138.5); 1.928 (88.3); 1.780 (0.5); 1.774 (0.9); 1.768 (1.1); 1.782 (0.8); 1.758 (0.4); 1.437 (13.0); 1.271 (1.0); 1.222 (1.0); 1.204 (1.9); 1.188 (0.9); 0.794 (1.7); 0.782 (8.4); 0.777 (7.2); 0.784 (7.9); 0.759 (5.7); 0.747 (2.4); 0.725 A0.3); 0.810 (2.4); 0.800 (7.1); 0.592 (7.5); 0.588 (6.7); 0.584 (5.9); 0.571 (1.7); 0.148 (0.4); 0.000 (88.0); -0.008 (5.2); 0.150 (0.4) Example l-T3-2: ‘H-NMR (400.0 MHz. CD3CN): 8: 8.131 (12.6); 8.084 (13.3); 7.735 (7.6); 7.729 (9.9); 7.710 (5.2); 7.704 (3.5); 7.689 (5.8); 7.683 (4.6); 7.537 (16.0); 7.514 (8.9); 7.493 (7.4); 7.458 (1.9); 4.140 (1.8); 4.124 (2.1); 4.117 (5.8); 4.100 (5.9); 4.093 (6.2); 4.077 (5.9); 4.069 (2.6); 4.053 (2.1); 3.914 (0.6); 2.891 (0.7); 2.773 (0.6); 2.480 (0.7); 2.475 (1 .3); 2.470 (1.8); 2.466 (1.3); 2.461 (0.7); 2.325 (0.4); 2.273 (1.9); 2.221 (979.0); 2.115 (79.7); 2.097 (1.4); 1.973 (3.4); 1.966 (10.4); 1.960 ; 1.954 (102.7); 1.948 (182.7); 1.942 (241.3); 1.936 (167.3); 1.930 (87.0); 1.783 (0.7); 1.777 (1.1); 1.770 (1.5); 1.764 (1.1); 1.758 (0.6); 1.437 (15.2); 1.296 (0.5); 1.270 (1.7); 1.222 (0.7); 1.204 (1.3); 1.186 (0.6); 0.146 (0.3); 0.008 (2.7); 0.000 (69.9); -0.008 (3.3) Example l-T3-3: 1H-NMR (400.0 MHz. : 6: 8.129 (2.6); 8.075 (2.6); 7.738 (1.6); 7.732 (2.0); 7.701 (1.1); 7.696 (0.8); 7.681 (1.2); 7.675 (1.1); 7.572 (0.5); 7.536 (3.2); 7.496 (1.8); 7.475 (1.5); 2.146 (33.6); 2.113 (16.5); 1.972 (0.4); 1.964 (2.4); 1.958 (5.6); 1.953 (29.5); 1.946 (53.8); 1.940 (72.5); 1.934 (50.1); 1.928 ; 1.769 (0.4); 1.599 (0.8); 1.585 (1.9); 1.578 (2.0); 1.564 (1.1); 1.437 (16.0); 1.359 (1.1): 1.345 (2.0); 1.338 (2.0); 1.324 (0.8); 1.269 (0.6); 0.008 (1 .9); 0.000 (51.3); -0.009 (2.0) Example I—T3-4: 1H-NMR (400.0 MHz. CD3CN): : 8.132 (5.7); 8.077 (8.1); 7.719 (3.4); 7.714 (4.3); 7.878 (2.2); 7.873 (1.8); 7.857 (2.8); 7.852 (2.3); 7.537 (7.8); 7.515 (1.0); 7.495 (1.0); 7.488 (4.3); 7.485 (3.3); 5.338 (0.9); 5.318 (1.8); 5.298 (1.8); 5.274 (1.0); 3.544 (2.3); 3.521 (4.7); 3.499 (3.1); 3.370 (3.0); 3.349 (4.8); 3.346 (4.3); 3.325 (2.4); 2.469 (0.4); 2.274 (0.4); 2.208 (300.4); 2.154 (0.5); 2.115 (38.2); 1.973 (1.3); 1.988 (3.0); 1.980 (8.3); 1.954 (30.3); 1.948 (55.1); 1.942 (73.7); 1.935 (52.5); 1.929 (28.5); 1.776 (0.4); 1.770 (0.5); 1.784 (0.4); 1.437 (18.0); 1.26 (1.6); 1.222 (0.3); 1.204 (0.6); 0.008 (0.7); 0.000 (20.8) e I-T3-5: ‘H-NMR (601.6 MHz. 003011): 8: 8.125 (8.3); 8.124 (8.5); 8.072 (9.3); 8.071 (9.2); 7.880 ; 7.877 (5.7); 7.888 (5.3); 7.884 (3.0); 7.537 (9.4); 7.485 (4.7); 7.482 (2.1); 7.473 (1.9); 7.470 (4.3); 7.481 (2.3); 2.148 (139.0); 2.113 (53.4); 2.080 (0.5); 2.058 (0.9); 2.052 (1.3); 2.048 (0.9); 2.044 (0.4); 1.988 (5.4); 1.958 (14.4); 1.953 ; 1.950 (93.5); 1.945 (188.8); 1.941 (244.5); 1.937 (162.8); 1.933 (81.9); 1.924 (1.3); 1.835 (0.5); 1.831 (0.9); 1.827 (1.4); 1.822 (0.9); 1.818 (0.5); 1.393 (2.4); 1.383 (5.5); 1.380 (5.9); 1.370 (3.2); 1.343 (0.4) 1 269 (0.8); 1.251 (1.3); 1.248 (1.4); 1.238 (4.5); 1.228 (1.0); 1.225 (1.0); 0.098 (0.4); 0.005 (3.0); 0.000 (105.8); -0.006 (3.3); -0.100 (0.4) Example l-T3-8: 'H-NMR (801.8 MHz. CD3CN): 8: 8.130 (11.9); 8.129 (12.8); 8.082 (13.1); 8.081 (13.4); 7.809 (8.6); 7.805 (9.0); 7.697 (5.1); 7.893 (4.8); 7.883 (59. ); 7.879 (5.7); 7.538 (13.8); 7.508 (9.3); 7.494 (8.0); 7.304 (1.1); 7.295 ( 1.9); 7.288 (1.1); 7.069 (1.2); 4.045 (16.0); 4.038 (15.9); 3.973 1. 8); 3.982 (1.8); 3.957 (5.2); 3.946 (5.2); 3.941 (5.5); 3.930 (5.3); 3.928 (2 .0) ; 3.915 (1.8); 2.220 (0.4); 2.153 ; 2.115 (73.8); 2.104 (1.0) ; 2.052 (0.4); 2.008 (0.4); 1.966 (1.4); 1.958 (3.8); 1.953 (4.5); 1.950 1 25.7); 1.945 (45.5); 1.941 ; 1.937 (48.1); 1.933 (22.7); 1.827 (0.4); 1.268 (1.1); 0.005 (0.8); 0.000 (28.7); -0.006 (0.9) Example I-T3—7: 1H-NMR (400.0 MHz. de—DMSO): 8: 9.043 (1.2); 9.038 (1.2); 8.803 (1.3); 8.798 (1.3); 8.672 (3.2); 8.648 (0.9); 8.638 (0.9); 8.405 (3.2); 8.390 (1.1); 8.384 (1.9); 8.379 (1.0); 8.316 (0.3); 7.602 (3.5); 3.902 (9.7); 3.330 (83.7); 3.243 (0.6); 3.169 (0.4); 2.903 (0.3); 2.893 (0.5); 2.885 (0.7); 2.875 (0.7); 2.867 (0.4); .857 (0.3); 2.676 (0.4); 2.672 (0.5); 2.667 (0.4); 2.525 (1.4); 2.512 ; 2.507 (61.4); 2.503 (80.2); 2.498 (57.8); 2.494 (27.6); 2.334 A 0.3); 2.329 (0.5); 2.325 (0.3); 2.131 (16.0); 1.909 (0.3); 0.763 (0.4); 0.750 (1.1); 0.745 (1.6); 0.733 (1.5); 0.727 (1.3); 0.716 (0.6); 0.619 (0.6); 0.608 (1.7); 0.602 (1.4); 0.598 (1.4); 0.593 (1.2); 0.580 (0.4); 0.000 (9.2) Example l-T3-8: 1H-NMR (400.0 MHz. de-DMSO): 8: 9.538 (2.0); 9.102 (1.4); 9.097 (1.4); 8.827 (1.4); 8.823 (1.5); 8.695 (3.2); 8.444 (1.1); 8.439 (1.9); 8.434 (1.2); 8.424 (3.3); 7.605 (3.8). 3.902 (6.0); 3.374 (0.4); 3.330 (90.4); 3.243 (0.4); 3.169 (2.1); 2.676 (0.4); 2.672(06); 2.667 (0.5); 2.542 (0.5); 2.507 : 2.503 (97.5); VN" /01’7‘47 — 2 . PCT/EPZOM/m3795 12.498 (74.7); 2.334 (0.4); 2.329 (0.6); 2.325 (0 5); 2.132 (16.0); 1.628 (0.7); 1.614 (2.0); 1.607 (2.1); 1.594 (0.9); 1.347 (0.9); 1.334 (2.1). 1.327 (2.1); 1.313 (0.7); 0.000 (8.2) Example 173—9; 1H—NMR (400.0 MHz. de-DMSO): 8: 8.508 (2.0); 8.506 (2.0); 8.473 (1.0); 8.463 (1.0); 8.276 (2.2); 7.895 (0.5); 7.876 (1.0); 7.861 (0.5); 7.592 (4.1); 7.399 (0.5); 7.383 (1.0); 7.368 (0.7); 7.305 (1.1); 7.286 (1.7); 7.266 (0.7); 3.902 (5.7); 3.330 ; 3.243 (0.4); 3.175 (0.4); 3.162 (0.3); 2.875 (0.4); 2.665 (0.5); 2.857 (0.7); 2.847 (0.7); 2.838 (0.5); 2.828 (0.3); 2.672 (0.5); 2.507 (63.9); 2.503 (80.2); 2.329 (0.5); 2.114 (16.0); 0.725 (0.4); 0.707 (1.8): 0.695 (1.7); 0.689 (1.5); 0.678 (0.8); 0.556 (0.8); 0.545 (1.8); 0.539 (1.8); 0.530 (1.6); 0.518 (0.5); 0.000 (6.1) Example 110: 1H-NMR (400.0 MHz. do—DMSO): : 9.369 (2.0); 8.535 (1.8); 8.532 (1.9); 8.290 (2.0); 7.968 (0.4); 7.965 (0.5); 7.949 (0.9); 7.946 (0.9); 7.931 (0.5); 7.927 (0.5); 7.595 (3.9); 7.479 (0.4); 7.475 (0.4); 7.459 (0.9); 7.443 (0.6); 7.440 (0.5); 7.352 (1.0); 7.333 (1.7); 7.314 (0.8); 3.903 (8.2); 3.372 (0.4); 3.329 (104.6); 3.243 (0.6); 3.175 (0.3); 2.675 (0.4); 2.871 (0.5); 2.667 (0.4); 2.541 (0.5); 2.507 (70.8); 2.502 ; 2.498 (68.7); 2.333 (0.4); 2.329 (0.5); 2.324 (0.4); 2.115 (16.0); 1.598 (0.8); 1.584 (2.0); 1.577 (2.1); 1.564 (0.9); 1.292 (0.9); 1.278 (2.1); 1.272 (2.2); 1.257 (0.8); 1.169 (0.3): 1.068 (0.4); 0.007 (0.4); 0.000 (7.5); -0.008 (0.4) Example 1—73—11: 1H-NMR (400.0 MHz. ds-DMSO): 8: 8.522 (0.9); 8.512 (0.9); 8.500 (3.3); 3.211 (3.2); 7.818 (1.8); 7.799 (1.8); 7.646 (1.8); 7.621 (1.8); 7.590 (3.5); 3.902 (3.1); 3.330 (117.7); 3.304 (0.3); 2.861 (0.3); 2.851 (0.4); 2.842 (0.7); 2.832 (0.7); 2.624 (0.4); 2.676 (0.4); 2.671 (0.5); 2.667 (0.3); 2.525 (1.5); 2.511 ; 2.507 (58.1); 2.502 (75.7); 2.498 (54.9); 2.493 (26.6); 2.334 (0.3); 2.329 (0.5); 2.324 (0.3); 2.127 (16.0); 0.733 (0.4); 0.720 (1.2); 0.715 (1.7); 0.703 (1.6); 0.697 (1.3); 0.685 (0.6); 0.575 (0.6); 0.564 (1.7); 0.558 (1.5); 0.554 (1.4); 0.548 (1.3); 0.536 (0.4); 0.000 (7.9) Example 1—73—12: 1H-NMR (400.0 MHz. O): 8: 9.396 (1.8); 8.522 (3.2); 8.223 (3.2); 7.906 (1 .6); 7.887 (1.6); 7.712 (1.6); 7.687 (1 .6); 7.593 (3.7); 3.903 (2.7); 3.332 (98.2); 2.672 (0.5); 2.542 (0.4); 2.507 (87.0); 2.503 (83.7); 2.498 (62.0); 2.334 (0.4); 2.329 (0.5); 2.325 (0.4); 2.129 (16.0); 1.604 (0.8); 1.590 (2.0); 1.583 (2.1); 1.570 (0.9); 1.312 (0.9); 1.299 (2.0); 1.292 (2.0); 1.278 (0.8); 0.000 (7.1) Example 3z1H—NMR (400.0 MHz. do-DMSO); 8: 8.514 (1.8); 8.510 (1.9); 8.480 (0.9); 8.470 (0.9); 8.285 (2.1); 8.228 (0.8); 8.220 (0.8); 8.207 (0.8); 8.202 (0.8); 7.767 (0.4); 7.762 (0.5); 7.755 (0.5); 7.749 (0.6); 7.746 (0.6); 7.740 (0.5); 7.734 (0.5); 7.728 (0.4); 7.595 (3.7); 7.402 (0.9); 7.380 (0.9); 7.375 (1.0); 7.354 (0.8); 3.902 (1.5); 3.444 (0.4); 3.425 (0.6); 3.405 (1.1); 3.353 (438.8); 3.292 (0.5); 3.273 (0.3); 2.864 (0.5); 2.855 (0.7); 2.846 (0.7); 2.837 (0.5); 2.827 (0.3); 2.878 (0.4); 2.673 (0.5); 2.669 (0.4); 2.509 (81.5); 2.504 (78.8); 2.500 (57.5); 2.335 (0.4); 2.331 (0.5); 2.327 (0.4); 2.121 (16.0): 0.746 (0.4); 0.733 (1.2); 0.728 (1.7); 0.716 (1 .8); 0.710 (1 .3); 0.699 (0.8); 0.802 (0.6); 0.592 (1 .7); 0.585 (1.6); 0.576 (1.3); 0.564 (0.4) Example 114: 1H—NMR (400.0 MHz. ds-DMSO): & 8.600 (1.8); 8.596 (1.8); 8.536 (1.1); 3.525 (1.1); 8.352 (1.9); 7.977 (1.6); 7.980 (1.6); 7.594 (3.7); 7.437 (1.7); 7.411 (1.7); 3.902 (4.8); 3.332 (129.0); 2.826 (0.4); 2.817 (0.7); 2.807 (0.7); 2.799 (0.4); 2.789 (0.3); 2.678 (0.4); 2.672 (0.5); 2.667 (0.4); 2.511 (32.0); 2.507 (61.8): .503 (79.3); 2.498 (57.6); 2.494 (28.2); 2.334 (0.3); 2.329 (0.5); 2.325 (0.4); 2.115 (16.0); 0.733 (0.4); 0.720 (1 .2); 0.715 (1 .6); 0.703 (1.5); 0.697 (1 .3); 0.685 (0.5); 0.567 (0.5); 0.557 (1.7); 0.551 (1.5); 0.547 (1.4); 0.541 (1.3); 0.529 (0.4); 0.000 (6.1) Example 1—T3-15: 1H-NMR (400.0 MHz. de-DMSO): 6: 8.711 (3.3); 8.694 (1.1); 8.684 (1.0); 8.450 (3.3); 8.369 (1.8); 8.174 (1.8); 7.971 (1.8); 7.601 (3.9); 3.903 (1.0); 3.331 (150.2); 2.910 (0.3); 2.901 (0.5); 2.892 (0.7); 2.882 (0.7); 2.874 (0.5); 2.865 (0.4); 2.672 (0.5); 2.507 (59.3); 2.503 (74.7); 2.499 (55.2); 2.334 (0.4); 2.33! (0.5); 2.133 (16.0); 0.769 (0.4); 0.755 (1.3); 0.751 (1.7); 0.738 (1.6); 0.733 (1.4); 0.721 (0.6); 0.630 (0.6); 0.620 (1.8); 0.613 (1.7): 0.604 (1 .4); 0.592 (0.4) Example l-T3-16: 1H-NMR (601.6 MHz. ds-DMSO): 8: 8.439 (0.8); 8.433 (0.9); 8.344 (3.1); 8.343 (3.2); 8.082 (3.2); 8.081 (3.3); 7.912 (1.7); 7.909 (1.7); 7.670 (0.9); 7.667 (0.9); 7.657 (1.0); .854 (1.0); 7.600 (3.4); 7.368 (1.3); 7.354 (1.2); 3.376 (0.5); 3.367 (1.1); 3.351 (401.9); 3.328 (0.5); 3.324 (0.5); 2.997 (3.2); 2.856 (0.4); 2.850 (0.7); 2.844 (0.7); 2.838 (0.4); 2.831 (0.3); 2.618 (0.4); 2.615 (0.6); 2.612 (0.4); 2.543 (5.5); 2.524 (1.0); 2.521 (1.3); 2.518 (1.2); 2.509 (30.4); 2.506 (87.4); 2.503 (93.3); 2.500 (68.5); 2.497 ; 2.438 (7.5); 2.390 (0.4); 2.387 (0.6); 2.384 (0.4); 2.146 (16.0); 0.715 (0.4); 0.707 (1.2); 0.703 (1.6); 0.895 (1.5); 0.692 (1.3); 0.684 (0.5); 0.590 (0.6); 0.583 (1.6); 0.579 (1.4); 0.576 (1.3); 0.572 (1.3); 0.584 (0.4); 0.000 (2.6) e 1-73—17: ‘H-NMR (400.0 MHz. de-DMSO): 8: 9.576 (0.4); 9.437 (2.3); 8.736 (0.7); 8.625 (1.7); 8.821 (1.8); 8.472 (0.7); 8.411 (0.4); 8.375 1.8); 8.372 (1.9); 8.316 (0.5); 8.243 (0.4); 8.030 (1.7); 8.013 (1.6); 7.993 (0.3); 7.597 (3.8); 7.547 (1.7); 7.521 (1.9); 4.036 (1.1); 3.903 (6.7); 3.630 (0.4); 3.623 (0.4); 3.614 (0.4); 3.608 (0.3); 3.597 (0.3); 3.392 (0.7); 3.332 (259.6); 3.287 (0.3); 3.175 (0.4); 3.162 (0.5); 3.155 (0.4); 3.145 (0.5); 3.138 (0.4); 3.127 (0.5); 3.056 (0.4); 3.022 (4.3); 2.751 (0.4); 2.690 (1.7); 2.676 (0.8); 2.672 (1.1); 2.867 (0.9); 2.525 (3.7); 2.511 (72.5); 2.507 (143.5); 2.503 (187.7); 2.498 (136.4); 2.494 (66.3); 2.338 (0.4); 2.334 (0.8); 2.329 (1.1); 2.325 (0.8); 2.134 (3.5); 2.116 (16.0); 1.614 (0.5); 1.607 (1.1); 1.593 (1.9); 1.586 (2.0); 1.573 (0.8); 1.344 (0.5); 1.337 (0.5); 1.310 (0.9); 1.296 (1.9); 1.289 (2. ); 1.274 (3.8); 1.259 (8.5); 1.244 (6.0); 1.225 (1 .2); 0.008 (0.5); 0.000 (16.5); 0.009 (0.5) Example l-T3-18: 1H—NMR (400.0 MHz. da-DMSO): 8: 9.576 (2.0); 8.736 (3.2); 8.472 (3.3); 8.411 (1.7); 8.316 (0.3); 8.243 (1.6); 7.994 (1.6); 7.605 (3.6); 3.903 (10.2); 3.372 (0.7); 3.333 (152.4); 3.243 (1 .3); 3.175 (0.4); 3.162 (0.4); 2.890 (0.4); 2.676 (0.4); 2.872 (0.6); 2.667 (0.4); 2.542 (0.6); 2.525 (1.9); 2.512 (39.2); 2.507 (77.8); 2.503 (101.6); 2.498 (73.7); 2.494 (35.7); 2.334 (0.4); 2.330 (0.6); 2.325 (0.4); 2.134 ; 2.116 (0.5); 1.629 (0.7); 1.614 (1.8); 1.607 (2.0); 1.594 (0.9); 1.358 (0.9); 1.345 (1.9); 1.338 (2.0); 1.323 (0.7); 1.259 (0.5); 1.244 (0.4); 1.017 (0.6); 1.001 (0.6); 0.000 (9.1) Example 1-73—19; 1H—NMR (400.0 MHz. de-DMSO); 8: 9.367 (1.9); 8.537 (1 .8); 8.534 (1.9); 8.300 (2.2); 8.277 (0.8); 8.271 (0.9); 8.259 (0.9); 8.253 (0.8); 7.796 (0.4); 7.791 (0.5); 7.784 (0.5); 7.778 (0.6); 7.775 (0.6); 7.769 (0.6); 7.763 (0.5); 7.757 (0.5); 7.598 (3.8); 7.457 (0.8); 7.435 (0.8); 7.430 (1.0); 7.409 (0.7); 3.903 (4.8); 3.335 (104.3); 2.672 (0.4); 2.542 (0.3); 2.507 (54.0); 2.503 (69.3); 2.499 (52.7); 2.330 (0.4); 2.122 (18.0); 1.609 (0.8); 1.595 (2.0); 1.586 (2.1); 1.575 (0.9); 1.323 (0.9); 1.309 (2.0); 1.303 (2.1); 1.288 (0.8); 0.000 (5.6) e 1—73—20: 1H-NMR (400.0 MHz. ds-DMSO): 88.816 (2.3); 8.810 (2.3); 8.695 (3.4); 8.881 (1.1); 8.670 (1.1); 8.451 (3.4); 8.184 (2.3); 8.178 (2.2); 7.601 (3.8); 3.903 (7.0); 3.333 (173.9); 3.289 (0.4); 3.242 (0.9); 3.175 (0.6); 3.182 (0.5); 2.859 (0.4); 2.850 (0.7); 2.840 (0.7); 2.832 (0.4); 2.822 (0.3); 2.676 (0.4); 2.671 72661(0.4); 2.542 (0.4); 2.511 (34.1); 2.507 (66.3); 2.502 (85.9);24981630); 2.494 (31.0); 2.333 (0.4); 2.329 £05); 2.325 (0.4); ‘WO 67647 — \.) U) l\) I , PCT/EPZOI4/O7379S 2132 (0.7); 2.117 (16.0); 1.016 (0.4); 1.001 (0.4); 0.755 (0.5); 0.742 ( .3); 0.737 (1.7); 0.725 (1.6); 0.719 (1.4); 0.707 (0.5); 0.564 (0.6)l 0.553 (1.7); 0.547 (1.6); 0.543 (1.5); 0.538 (1.4); 0.528 (0.4); 0.000 (7.1 Example 1; 1H-NMR (600.1 MHz. 8501150) 9.593 (1.8); 8.868 (2.3); 8.864 (2.3); 8.709 (3.3); 8.456 (3.4); 8.262 (2.3); 8.258 (2.2); 7.603 (3.7); 3.388 (0.4); 3.383 (0.4); 3.381 (0.5). 3.369 (0.8); 3.340 (1164.0); 2.994 (0.7); 2.617 (0.6); 2.615 (0.8); 2.612 (0.6); 2.542 (39.9); 2.523 (1.4); 2.520 (1.7); 2.517 (1.8); 2.508 ; 2.505 (103.1); 2.502 (140.8); 2.499 (100.9); 2.497 (46.2); 2.389 (0.6); 2.388 (0.8); 2.383 (0.6); 2.117 (16.0); 1.636 (0.8); 1.627 (2.0); 1.622 (2.1); 1.613 (0.8); 1.288 (0.9); 1.278 (1.9); 1.274 (2.1); 1.264 (0.8); 0.005 (0.8); 0.000 (21.9); 0.006 (0.7) Example 1—13—22: 1H-NMR (400.1 MHz. do-DMSO): : 9.397 (6.5); 8.882 (5.3); 8.677 (5.1); 8.405 (7.9); 8.368 (0.3); 8.087 ; 8.060 (0.3); 8.041 (0.7); 7.981 (1.7); 7.986 (2.6); 7.968 (2.7); 7.948 (1.5); 7.944 (1.4); 7.763 (0.3); 7.505 (1.2); 7.501 (1.3); 7.486 (2.7); 7.470 (1.8); 7.466 (1.6); 7.384 (0.6); 7.374 (3.1); 7.365 (1.1); 7.355 (5.1); 7.345 (0.8); 7.336 (2.3); 5.761 (0.8); 3.348 (68.6); 3.028 (1.2); 2.875 (1.0); 2.712 (0.4); 2.671 (0.3); 2.542 (99.6); 2.507 (38.4); 2.502 (50.3); 2.498 (38.2); 2.368 (0.4); 2.087 (0.3); 1.801 (2.4); 1.587 (6.3); 1.580 (6.5); 1.567 (2.8); 1.288 (3.1); 1.275 (6.2); 1.268 (6.6); 1.254 (2.5); 1.234 (0.8); 1.169 (0.9); 0.146 (0.3); 0.000 (72.5); -0.008 (4.9); 0.150 (0.4) Example 123: 1H-NMR (400.0 MHz. CD3CN): : 8.202 (5.5); 8.187 (0.5); 8.161 (5.9); 8.146 (0.5); 7.931 (0.4); 7.900 (9.0); 7.886 (0.8); 7.739 (3.5); 7.734 (4.4); 7.720 (0.5); 7.707 (2.8): 7.701 (1.9); 7.686 (3.0); 7.680 (2.5); 7.648 (1.5); 7.507 (4.1); 7.486 (3.4); 4.360 (0.5); 4.342 (0.5); 4.086 (1.0); 4.068 (2.9); 4.050 (3.0); .032 (1.1); 2.162 (61.1); 2.149 (10.3); 2.120 (0.4); 2.114 (0.4); 2.108 (0.5); 2.102 (0.4); 1.972 (13.4); 1.965 (4.8); 1.959 (8.2); 1.953 (30.5); 1.947 (52.3); 1.940 (68.1); 1.934 (48.2); 1.928 (27.3); 1.769 (0.4); 1.596 (1.8); 1.581 (4.5); 1.574 (4.4); 1.561 (2.8); 1.437 (16.0); 1.422 (1.2); 1.401 (0.5); 1.371 (0.6); 1.361 (2.8); 1.353 (1.9); 1.347 (4.6); 1.341 (4.6); 1.336 (1.5); 1.326 (2.3); 1.268 (1.6); 1.222 (3.7); 1.204 (7.2); 1.186 (3.8); 0.000 (2.2) Example l-T3-24: 1H-NMR (600.1 MHz. CD3CN); 8: 8.189 (6.2); 8.144 (6.7); 7.897 (10.1); 7.690 (3.8); 7.687 (4.5); 7.652 (2.6); 7.648 (2.1); 7.638 (2.8); 7.634 (2.4); 7.471 (4.4); 7.457 (3.7); O).891 (1.0); 5.446 (2.0); 4.077 (2.0); 4.065 (6.2); 4.053 (6.2); 4.041 (2.1); 2.864 (0.8); 2.857 (1.1); 2.852 (1.7); 2.845 (1.7); 2.839 (1.1); 2.833 (0.8); 2.129 (55.4); 2.054 (0.5); 2.050 (0.7); 2.046 (0.5); 1.971 (27.5); 1.963 (6.3); 1.955 (8.8); 1.951 (10.1); 1.947 (46.9); 1.943 (78.2); 1.939 (115.2); 1.935 (77.9); 1.931 (39.3); 1.922 (0.5); 1.828 (0.4); 1.824 (0.6); 1.820 (0.4); 1.437 (16.0); 1.270 (0.4); 1.216 (7.4); 1.204 (14.6); 1.192 (7.3); 0.786 (1.0); 0.777 (2.8); 0.774 (3.6): 0.765 (3.6); 0.762 (2.7); 0.754 (1.2); 0.606 (1.1); 0.599 (2.9); 0.598 (2.9); 0.595 (3.0); 0.591 (2.8); 0.588 (2.8); 0.580 (0.9); 0.005 (2.1); 0.000 ; -0.006 (2.2) e 125: 1H-NMR (601.6 MHz. 0133051): : 8.201 (9.9); 8.163 (10.8); 7.899 (16.0); 7.738 (5.9); 7.734 (7.4); 7.710 (4.2); 7.706 (3.3); 7.696 (4.6); 7.693 (4.0); 7.522 (6.8); 7.508 (5.8); 7.328 (1.4); 7.265 (0.6); 7.251 (1.5); 7.239 (1.1); 7.195 (1.4); 7.183 (1.0); 7.162 (0.5); 7.150 (0.7); 5.446 (1.0); 4.127 (1.3); 4.116 (1.5); 4.111 (4.2); 4.100 (4.3); 4.095 (4.5); 4.085 (4.3); 4.080 (1.7); 4.069 (1.4); 2.328 (5.9); 2.134 (32.5); 2.132 (53.6); 2.058 (0.4); 2.054 A0.8); 2.050 (1.0); 2.046 (0.7); 1.971 (1.2); 1.964 (7.9); 1.955 (12.2); 1.951 (13.8); 1.947 (67.1); 1.943 (113.1); 1.939 (165.4); 1.935 (111.4); 1.931 (56.0); 1.833 (0.5); 1.829 (0.7); 1.825 (0.9); 1.821 (0.7); 1.437 (5.7); 1.269 (0.8); 1.204 (0.6); 1.192 (0.3); 0.000 (1.4) Example l-T3-26: 1H-NMR (601.6 MHz. co3cw); : 8.222 (8.5); 8.184 (9.2); 8.183 (8.4); 7.933 (13.8); 7.743 (5.6); 7.739 (6.7); 7.712 (3.8); 7.709 (3.0); 7.699 (4.2); 7.695 (3.6); 7.530 (6.3): 7.516 (5.4); 7.228 (0.3); 7.216 (0.4); 7.172 (1.1); 5.481 (0.5); 4.022 (0.9); 3.653 (2.8); 3.641 (6.5); 3.831 (6.8); 3.620 (2.9); 2.605 (0.6); 2.594 (1.2); 2.588 (2.0); 2.582 (0.9); 2.575 (3.7); 2.568 (2.2); 2.584 (2.1); 2.558 (3.9); 2.549 (0.9); 2.545 (2.0); 2.538 (1.3); 2.527 (0.6); 2.505 (0.6); 2.502 (1.0); 2.499 (1.4); 2.496 (1.0); 2.361 (1.2); 2.218 (233.1); 2.214 (233.8); 2.213 ); 2.211 (239.7); 2.210 (216.4); 2.208 (358.9); 2.092 (0.7); 2.088 (1.2); 2.084 (1.6); 2.080 (1.2); 2.076 (0.6); 2.005 (1.3); 1.998 (14.1); 1.990 (21.9); 1.985 ; 1.982 (121.7); 1.978 (205.2); 1.973 (304.1); 1.969 (210.4); 1.965 (107.9); 1.867 (0.7); 1.883 (1.2); 1.859 (1.7); 1.855 (1.2); 1.850 (0.6); 1.470 (16.0); 1.303 (0.4); 1.237 (0.6); 0.033 (1.8) Example l-T3-27: 1H-NMR (400.0 MHz. do~DMSO): 8: 9.439 (6.6); 8.693 (9.5); 8.441 (9.4); 8.317 (0.9); 8.274 ; 7.807 (2.2); 7.802 (3.8); 7.792 (5.8); 7.786 (9.9); 7.589 (5.1); 7.553 (1.2); 7.546 (4.2); 4.020 (0.3); 3.568 (10.9); 3.328 (401.1); 2.675 (2.2); 2.671 (2.9); 2.668 (2.2); 2.508 (372.0); 2.502 (465.0); 2.497 (338.4); 2.333 (2.3); 2.328 (2.9); 2.324 (2.1); 1.989 (1.3); 1.615 (2.4); 1.601 (6.2); 1.594 (6.2); 1.581 (2.5); 1.398 (5.4); 1.287 (2.8); 1.274 (6.1); 1.267 (6.2); 1.253 (2.2); 1.235 (0.4); 1.192 (0.4); 1.175 (0.7); 1.157 (0.4); 0.146 (0.7); 0.000 ); 0.008 (7.8); 0.150 (0.8) Example l-T3-28: 1H-NMR (400.0 MHz.d11-DMSO): 8: 8.684 (0.4); 8.672 (9.5); 8.535 (3.2); 8.524 (3.2); 8.453 (0.3); 8.427 (9.5); 8.271 (16.0); 7.749 (2.3); 7.744 (3.3); 7.723 (12.2); 7.519 A4.6); 7.498 (3.9); 4.056 (0.5); 4.038 (1.4); 4.020 (1.4); 4.002 (0.5); 3.568 (7.8); 3.329 (74.2); 2.857 (0.9); 2.848 (1.3); 2.839 (1.9); 2.829 (2.0); 2.820 (1.3); 2.811 (0.9); 2.801 (0.3); 2.676 (0.4); 2.671 (0.6); 2.667 (0.4); 2.524 (1.5); 2.511 (34.6); 2.507 (68.9); 2.502 (89.7); 2.498 (64.3); 2.493 (30.8); 2.333 (0.4); 2.329 (0.6); 2.324 (0.4); 1.989 (6.1); 1.397 (15.9); 1.193 (1.6); 1.175 (3.1); 1.157 (1.6); 0.728 (1.3); 0.716 A3.7); 0.711 (4.9); 0.698 (4.7); 0.693 (3.9); 0.681 (1.6); 0.561 (1.7); 0.551 (5.1); 0.544 (4.7); 0.535 (4.1); 0.523 (1.2); 0.008 (1.4); 0.000 (37.7); -0.008 (1.4) Example l—T3-29: 'H-NMR (400.1 MHZ. ds—DMSO) 8: 9.042 (6.2); 9.036 (6.0); 8.962 (0.4); 8.831 (6.4); 8.826 (6.3); 8.807 9.8); 8.678 (3.3); 8.668 (3.2); 8.507 (9.6); 8.478 (0.5); 8.385 (3.9) 8.379 (6.4); 8.374 (3.5); 8.111 ; 3.368 (0.3); 3.367 (0.3); 3.365 (0.4); 3.362 (0.5); 3.361 (0.6); 3.360 (0.6 ): 3.357 (0.7); 3.356 (0.8). 3.350 (1.8); 3.330 (278.8); 3.313 (3.5); 3.309 (2.7); 3.308 (2.6); 3.306 (2.5); 3.297 (1.0); 3.295 (1.0); 3.294 (0.9); 3.287 (0.6); 3.284 (0.5); 3.281 (0.4); 3.279 (0.4); 3.277 (0.4); 2.915 (0.4); 2.905 (1.0); 2.896 (1.5); 2.887 (2.2); 2.877 (2.3); 2.869 (1 .5); 2.859 ( 1 . 1): 2.849 (0.4;) 2.711 (0.4); 2.671 (0.3); 2.565 (0.4); 2.564 (0.5); 2.583 (0.5); 2.562 (0.6); 2.560 (0.7); 2.559 (0.8); 2.558 (0 . . 9 ); 2.557 ( 1 . 1); 2.555 (1.4) . 2.542 (109.1); 2.533 (2.6); 2.532 (2.3); 2.530 (2.0); 2.529 (1.9); 2.528 (1.8); 2.527 (1.8); 2.525 (1.9); 2.524 (2.0) 2.523 (2.0); 2.511 (15.9); 2.507 (30.0); 2.502 ; 2.498 (28.5); 2.494 (14.2); 2.368 (0.4); 2.130 (0.7); 1.234 (0.5); 0.765 (1 .4); 0.752 (4.2); 0.747 (5.5); 0.735 (5.4); 0.729 (4.4); 0.717 (2.0); 0.696 (0.3); 0.618 (2.1); 0.608 (5.9); 0.602 (5.4); 0.592 (4.5); 0.580 (1.5); 0.146 (0.5l; 0.022 (0.4); 0.021 (0.5); 0.020 (0.6); 0.019 (0.7); 0.017 (0.7); 0.016 (0.9); 0.008 (6.5); 0.000 (110.7); 0.009 (5.4); 0.013 (2.0); 0.014 (1.7); 0.015 (1.6); 0.016 (1.4); 0.018 (1.3); 0.019 (1.2); 0.020 (1.1); 0.021 (1.0); 0.023 (1.0); 0.024 (0.9); 0.025 (0.9); 0.026 (0.8); 0.027 (0.7); 0.029 (0.7); . 0.031 (0.5); 0.034 (0.5); 0.035 (0.4); —0.036 (0.4); 0.150 (0.5) Example 1-13—30; 1H-NMR (400.1 MHz. ds-DMSO): : 9.562 (6.5); 9.101 (6.1); 9.095 (6.1); 8.989 (0.4); 8.855 (6.3); 8.850 (6.4); 8.829 (9.9); 8.5253 (9.7); 8.5245 (9.7); 8.496 (0.5); 8.438 (3.7); 8.432 (8.4); 8.427 (3.6); 8.115 (16.0); 5.759(05); 3.361 (0.8); 3.329 (283.9); 2.712 (0.5); 2.671 (0.4); 2.568 (0.3); 2.567 (0.4 ; 2.565 V1.70 2015/067647 — Q DJ (J) I 1104); 256410.51.) 2563105) 2562 (06) 2560107) 2559107) 2.558 10 9) 2.55711.0) 2.555 (1.2) 25 15) 2.542 (137.6); 2533 12.7);2.532122).2530120).2529119) 8); 2.52711.7);2525(18);252411 8) 2523119). 251162) 2.507 (31.6) 2.502 141 8). 2.4981306) 2493115 2) 2368105) 1.8311 12.6); 1.617165); 1 61016.6); 1.597130) 1.34813 1)1334166) 1328166) 1313 (..5). 1234104) 0146105) 3) 04); 0.024104); 0022105) 0.0211 10.6);0.02010.6); 0019 10. 7); 0.016109) 0.008 158;) 0000 11097) 0.008 149) 0014113) 0.015112); 0.016111); —0.01811.0);0.01910.9);002019;) 0.023107),-0.024106);- 0025 (0. 6); 0.027 10. 5); 0.029 10.4); 0.030 (0.4); 0.031 10.4); 0.150105) Example 1—13-31; ‘H-NMR (601.6 MHz. 003011): 6:19.953 10.4); 8.476 10.6); 8.461 (16.0); 8.193 10.3); 8.170 (0.6); 8.156 (14.9); 8.148 105) 8.0.5210 3); 7934171);7.931 (7.2);7901 .6); 7.866 15.7); 7.852 18.0);7.77914.3); 7.765 (3.1); 7.707 (9.8); 7.7031115); 7.689 (0.7;) 7669 (65) 7.665 (5.3); 7.655 173); 7.651 (6.3); 7.609104); 7.4771110); 7.463195); 6.905 12.4);3912121); 2.873106); 2.866119); 2860127) 2854 (41) 2.84814); 2842 (2.7); 20); 2.830 10.7); 2.145 (513.7); 2.068 (0.6); 2.064 10.6); 2.060 13.3); 2.05615); 2.052181) 56) 29); 1.966 (31.6); 1.958 (83.8); 1.9531984); 1.950 ); 1.945 (964.6); 1.941 (1429.4); 1.937 (989.8); 193315038); 1.925 18.1); 1. 843 103) 1.835130); 1.831 15.4); 79); 1.823154); 1.818127) 1.340103) 1.28510.7) 1269129); 1.123 10.4); 0.882 10.7); 0. 790 (2 5); 0.782 (6.8); 0.779 (9.4); 0.770 (9.0); 0.767 (7.4); 0.759 (3.0) 04); 0732104); 0.636 (0.4); 0.609129); 0.601 (7.4); 0 598 (78); 0.595 (7.3); 0.592 17.5); 0.583 12.4); 0.097 12.5);00051175); 0.000 (5984). 0.006 (20. 1); 0.100125) Example 1—73-32: 1H-NMR 1601.6 MHz. 003cm; 8: 19.978 (0.8); 8.505 (16.0); 8.234 (0.7); 8.197 (15.1); 7.962 (7.3); 7.933 (1.0); 7.901 (6.0); 7.887 (8.2); 7.812143); 7.798 (3.2); 7.785 (9.;1) 7.781 111. 3); 7.755 16.0); 7.752148) 7.742 (6.5); 7.738 (5.8); 7.557 (10.5); 7.543 (9.3); 7.451 (1.9); 7.284 (1 2:) 7.272 10.9); 7.228 11.1); 7.0.21619;) 7.183106) 5.04811.6); 4162120) 4.151 (2.;3) 4147166) 4136165) 4.131 (72);4.120165;) 4.115130); 4.104 122); 3.0946(. 8;) 2.49711. 3;) 2.361 (47;) 2.21111141);22081135.0).2.2.;0311586) 220011409). 2. 1981164.0;) 2.092108); 2.08. 11.1); 2.084(1-16;) 2.080111); 1997 127) 19891196) 19851223) 1.981 (1083) 1977 (1814). 1973 1268.0); 1.96911844); 1.965 (94. 6); 1.862 (1 0;) 1.858 (15 ;1854 ( 1.1); 1.303111); 0.033 (2.1) Example I-T3-3321H-NMR (601.6 MHZ. CDSCN): : 8.489 ) 8.221 (0.;7) 81841100) 7.966148) 7932111); 7902140); 7.886 (5.4); 7.813 130) 7.799 (2.;1) 7.759 (6.4) 7.755 (73) 7.725 14.;1) 7.722 (3. 2) 7.712 (4.;4) 7.708 (35) 7.533 170) 7519 (5.9); 7.111 (1.4); 3.659 134) 3.648 (77;) 3.637176); 3.626 (3. 3). 2.609 (0.8) 2.598114); 2.591 123) 2.579 (44); 125) 2568 12.5); 2.561 14.4); 2.549 12.4); 2.542 (1.5) 2.531 108) 2.184 1375.;5) 2.182 (3244;) 2181 (324.2) 2177 (3947;) 2.41731449). 2.092112); 208812.;1) 2.084 133) 2080 12.2) 2.076 11.1); 1.998 (27.5); 1.990 (42.2);1985 147.1); 1.981 (234.7); 1.977 13932) 1973 (581.0) 196914008) 1965107.); 1.867112); 1.863122) 1859 (3.3); 1.855 (2.2); 12); 1.471 116.0); 1.303 (1.3); 0.03313.4) Example 1-73—34; 1H-NMR (400.0 MHz. CD3CN): : 8.493 116.0); 8.193 (15.4); 8.099 (0.;4) 8.087 (6.7); 8.065 (8.0); 7.850 (4.4); 7.827 14.3); 7.815 17. 2). 7.752 (9.3) 7.7471116); 7.720 (6.3); 7.715 (4.4); 7.699 (7.2); 7.694 (58) 7.569 (4.2); 7.514 (10.8); 7.493 (8.8); 4.012 108) 3.891 105) 3.458 10. 5); 3.452 10 5) 3.236 (1.8); 3.067 (0.5); 3.056 10.5); 2.848 10.4) 214011151); 2.12011.0);2.11411.4); 2.108 (1 6.) 2102112); 06); 1.972117); 1.965 (8.4); 19581210); 195311038)94.711859); 1.940 (2459;) 669); 19281845) 1.781106) 1775111); 1769115); 1.763 11.0); 1.756106); 1.605146); 1.591 111.9;) 1.584111. 8) 1570160) 1530108) 2) 0.7) 1.36716.3) 13531118); 1.34 112.0);1.332(4.7);1.29410.6);1.26915. 1) 1204106) 6)‘0.146112);0..008(115); 000012820)-0.009197); 0150113) Example 1—73-35: 1H-NMR (400.0 MHz. CDSCN): 8:8.496 10. 7); 8.480 (160) 8.182 (153); 8.181 1148) 8.087166) 8.065179); 7.848 (47); 7.825 (4.;8) 7.812 (7.7); 7.702 (9.9); 7.697 1119;) 7670169)7664149)7649178) 7643163)7.481 (10.;8) 7460186) 6929129) 7)2.2.8771) 2868129)2.859 (45) 2.849145); 2.841 12.9); 2.831 (2.11) 2822(0.;7) 24.;67(04) 2..;463105) 24.;58104) 2..;15311888) 2..;120108) 1. 1); 2.108 11.3); 2102109) 2096105); 1972122) 1965187) 19591233); 19531957) 194711677) 1.941 (2156) 193411464); 19281731) 1781105); 0 9) 1769112); 1763108) 1757104) 1437169) 1269106); 1204105) 0800124) 0788 (77); 0783197) 7701102) 0765173) 0.753131) 0.731 (0.;4) 07.13104) 0656104) 0.646104); 0.617133); 0.6.;05187) 0599192) 059518.13) 0.590(7.6);0.57712.2); 0.522 (0.3); 0.146110); 0.000 (233.4); 0.009 19.6); 0.150 (1.0) Example I-T3-36: 1H-NMR (400.0 MHz. CDSCN): :8.496 (16.0); 8.1921153); 6 .4); 8.071 (7.7;) 7.850143); 7.827143); 7.814171); 7.74919.1);7.743111.5); 7.726168); 7.721 (4.1); 7.706 17.6); 7.700 15.6); 7.5321103); 7.511 18.3); 7.340 12.4); 4.149 12.3);4132 12.8); 71); 4.109 17.4); 4.102 (7.4); 4.085 (7.2); 4.078 (2.6); 4.061 12.3); 2.137 (51.6); 2.120106); 2114109);210811.0); 2.102 10.7); 2.095 (0.4); 1.965167); 1.9581182); 11.953 (74.7); 194611296); 194011659); 1 93411118); 19281554); 1.781 (04); 1.775107); 1.769110); 1.763 (0.6); 1.437137); 03); 0.146 10.8);0.008111.2);0.000 1188.1);-0.009 16.3); 0.150108) Example I-T3-37: 1H—NMR 1400.0 MHz. CDSCN): 8: 8.518 10.5); 8.490 116.0); 8.238 (0.5); 8.193 ; 8.090 16 7.); 8.069 17.7); 7.850 (4.2); 7.827 (4.0); 7.814 16.7); 7.735 (9.2); 7.729 111.3); 7.717104); 7.696 16.1); 7.690 14.5); 7.675 (7.0); 7.6691 .;9) 7.587104); 7.536103); 7.514106); 110); 7.494 (0.6);7.483 19.1); 7.459 (1.7); 7.445116); 6.694 10.4); 6.666 (0.3); 5.364 10 .;6) 5.343 12.4); 5.322 (4.7); 5.301 14.6); 5.280 (2.4); 5.259 (0.7); 4.006 .5);3.58910.4); 3.567 (0.4); 3.549 16.1); 3.545 (3.8); 3.525111 .4); 3.507 (4.3); 3.503179); 3.379 (8.1); 3.375 (5.1); 3.358 111.5); 3.355 (10.8); 3.338 13.6); 3. 334 (6. 2); 3.067 10. 5); 2.848 10.5); 2.472 (0. 5). 2.468110); 2.463 (1.3); 2.458 11.0); 2.453 10.5); 2.264 (0.3); 2.245 .4); 2. 151 (305.9); 2. 12011. 6). 2. 11412. 3); 2. 10712. 8); 2. 101 (2.0); 2.09511. 0); 2.022 11. 9); 2.003 10. 5); 1.964 (14. 6); 1.958 (33. 8), 1.952 1185. 3); 1.946 (333.6); 1.940 (449. 3); 1.934 (307.4); 1. 928 (157. 3); 1.915 (1.;9) 1.781 (1. 0); 1.775 (1. 8); 1. 768 12. 5); 1 76211.7); 1.756 (0.8); 1269 (2.1); 0.146 (3.1;) 0.025 107); 0.008 (22.9); 0.000 (696. 9). -0.009 (23 3); -0. 150 (3. 1) Example | -T-338. 11-l—NMR (400.0 MHz. CD3CN): 8: 8.238 (7.9); 8.119 (7.5); 7.748 (4.6); 7.742 15.7); 7.729140); 7.711 (3.1); 7.706 (2.3); 7.690 (3.5); 7.685 (2.8); 7.666 (1.4); 7.644 12.6): 7.595 15.4); 7.574 14.0); 7.500 15.1); 7.479 14.2); 4.068 11.0); 4.050 11.0); 4.032 10.3); 2.800 11.9); 2.781 15.9); 2.762 16.0); 2.744 (2.0); 2.139 (27.7); 05); 2.113 10.5); 2.107106); 2.101 (0.4); 1.972146); 1.964 (2.9); 1.958 17.5); 1.952 (33.5); 1.946 (58.9); 1.9401773): 1.933 153.2); 1.927 (27.2); 1.774104); 1.768 10.5); 1.762103); 1.601 (2.2); 1.587160); 1.580160); 1.566 (3.0); 1.526 10.4); 1.402103); 1362130); 1348160); 1); 1327123); 1270 (1.6); 1.221 11.2); 1.204123); 1.186111); 1.113177); 160); 1.076174); 11);00081137) 000012315); 00091107) 0150 (1.1) Example I -T-339:1H—NMR (400.0 MHz. : o: 8.226 18. 7); 8.120 10.4); 8.108 (8.2); 7.726 (4.1); 7.700 (4.7); 7.694 (5.9); 7.680 (0.5); 7.663 (4.5); 7.6fl135); 7.642 16.1); 7.637 (5.3); VVO 2015/067647 — [Q m .1; l 2014/073795 7.593 (5.2); 7.572 (2.8); 7.457 (5.5); 7.447 (4.5). 5.927 (1.4); 3.874 (0.7). 3.051 (0.4): 2.938 (0.4); 2.875 (0.9); 2.855 (1.4); 2.857 (2.1); 2.847 (2.1); 2.838 (1.4); 2.829 (1.0); 2.819 (0.3); 2.798 (2.0); 2.780 (5.2); 2.751 (5.4); 2.742 (2.2); 2.453 (0.4); 2.150 (108.1); 2.120 (0.8): 2.114 (0.9); 2.108 (1.0); 2101 (0.7); 2095 (0.4); 1972 (0.5); 1.954 (3.4); 1.958 (8.7); 1 952 (475); 1.945 (85.2). 1.940 (115.8); 1.934 ; 1.928 (41.7); 1.781 (0.4); 1.775 (0.5); 1.758 (0.7); 1.752 (0.5); 1.437 (5.5); 1.270 (1.4); 1.112 (7.8); 1.102 (1.0); 1.093 (15.0); 1.074 (7.5); 0.797 (1.2); 0.784 (3.7); 0.779 (4.7); 0.755 (4.9); 0.751 (3.7); 0.749 (1.7); 0.514 (1.5); 0.502 (4.5); 0.595 (4.5); 0.592 (4.0); 0.587 (4.0); 0.574 (1.2); 0145 (1.3); 0.008 (10.2); 0.007 (10.2); 0.000 (255.8); 0.008 (11.5); 0.150 (1.3) Example 0; ‘H-NMR (400.0 MHz. CDBCN): 8: 8.241 (8.2); 8.240 (8.8); 8.117 (8.2); 7.745 (4.5); 7.741 (5.2); 7.727 (4.2); 7.718 (3.5); 7.712 (2.4); 7.597 (3.5); 7.591 (3.1 ); 7.554 (1.4); 7.542 (2.5); 7.597 (5.2); 7.575 (2.7); 7.515 (5.5); 7.495 (4.5); 7.352 (0.9); 4.144 (1.2); 4.128 (1.3); 4.121 (3.5); 4.104 (3.5); 4.097 (3.8); 4.081 (3.5); 4.074 (1.4); 4.057 (1.2); 2.800 (2.0); 2.781 (5.2); 2.753 (5.3); 2.744 (2.1); 2.153 ; 2.149 (14.3); 1.971 (0.5); 1.954 (1.3); 1.958 (3.1); 1.952 (15.8); 1.945 (30.8); 1.940 ; 1.934 (28.7); 1.927 (14.8); 1.435 (10.4); 1.258 (0.4); 1.114 (7.8); 1.095 (15.0); 1.075 (7.5); 0.145 (0.5); 0.008 (4.4); 0.000 (115.7); -0.008 (5.1); 0.150 (0.5) Example l-T3-41: 1H-NMR (400.0 MHz. CD3CN) : : 8.239 (7.9); 8.122 (7.5); 7.732 (8.1); 7.727 (9.3); 7.589 (3.0); 7.584 (2.4); 7.558 (4.5); 7.553 (4.2); 7.544 (2.5); 7.598 (4.8); 7.577 (2.5). .491 (5.3); 7.470 (4.9); 5.342 (1.2); 5.320 (2.4); 5.300 (2.4); 5.279 (1.2); 3.548 (3.0); 3.524 (5.0); 3.502 (4.1); 3.374 (4.1); 3.371 (2.5), 3.354 (5.0); 3.351 (5.5); 3.330 (3.2); 2.803 (1.9); 2.784 (5.9); 2.755 (5.0); 2.745 (2.1); 2.458 (0.8); 2.454 (0.9); 2.459 (0.7); 2.155 (335.8), 2.120 (1.5); 2.114 (2.0); 2.107 (2.3); 2.101 (1.5); 2.095 (1.0); 1.954 (10.5); 1.958 (27.4); 1.952 (132.9); 1.945 (239.9); 1.940 (315.5); 1.934 (221.8); 1.928 (114.5); 1.781 (0.8); 1.775 (1.4); 1.759 (1.9); 1.752 (1.3); 1.755 (0.7); 1.437 (0.8); 1.259 (2.2); 1.115 (7.5); 1.095 (15.0): 1.078 (7.4); 0.145 (3.8); 0.008 (39.2); 0.000 (832.5); -0.008 (44.8); 0.150 (4.0) Example 1—73-42: ‘H-NMR (400.0 MHz. de-DMSO): 8: 8.830 (5.8); 8.821 (4.0); 8.815 (4.0); 8.594 (1.8); 8.583 (1.8); 8.548 (5.3); 8.547 (5.5); 8.315 (0.5); 8.192 (4.1); 8.185 (3.9); 8.107 (8.4); 3.902 (15.0); 3.333 (334.0); 3.243 (1.4); 3.175 (0.9); 3.152 (0.9); 2.870 (0.5); 2.851 (0.7); 2.852 (1.1); 2.842 (1 .1); 2.833 (0.7); 2.824 (0.5); 2.580 (0.3); 2.575 (0.7); 2.572 (0.9); 2.557 (0.7); 2.552 (0.3); 2.542 (0.5); 2.525 (2.7); 2.511 (58.5); 2.507 (115.5); 2.502 (152.5); 2.498 (110.8); 2.493 (53.8); 2.338 (0.3); 2.334 (0.7); 2.329 (0.9); 2.325 (0.7); 1.909 (0.5); 1.015 (0.5); 1.001 (0.5); 0.757 (0.7); 0.744 (2.0); 0.739 (2.8); 0.727 (2.5); 0.721 (2.2); 0.709 (0.9); 0.555 (0.9); 0.555 (2.5); 0.549 (2.4); 0.545 (2.3); 0.540 (2.2); 0.528 (0.7); 0.008 (0.5); 0.000 ; 0.009 (0.5) Example 3: ‘H-NMR (400.0 MHz. 56-01180); : 9.503 (7.1); 8.875 (5.9); 8.870 (5.9); 8.843 (10.4); 8.833 (0.4); 8.554 (10.3); 8.315 (0.8); 8.280 (7.0); 8.274 (5.8); 8.110 (15.0); 3.903 (14.5); 3.434 (0.4); 3.333 (555.4); 3.045 (0.5); 2.859 (0.5); 2.575 (1.3); 2.571 (1.7); 2.557 (1.3); 2.552 (0.7); 2.542 (1.5); 2.524 (5.5); 2.511 (105.5); 2.507 (205.5); 2.502 (255.2); 2.498 (191.5); 2.493 (91.5); 2.338 (0.5); 2.334 (1.1); 2.329 (1.5); 2.325 (1.1); 1.543 (2.4); 1.529 (5.7); 1.522 (5.0); 1.509 (2.5); 1.298 (2.9); 1.284 (5.7); 1.277 (5.1); 1.253 (2.3); 1.249 (0.4); 1.235 (0.4); 0.008 (0.8); 0.000 ; 0.009 (0.7) Example I-T3-44: ‘H-NMR (400.0 MHz. CD3CN): : 8.115 (9.4); 8.071 (10.0); 7.590 (5.4); 7.585 (5.3); 7.558 (1 .1); 7.553 (3.9); 7.532 (4.2); 7.585 (0.3); 7.549 (8.1); 7.509 (0.4); 7.453 (5.5); 7.442 (4.5); 5.895 (2.5); 4.058 (0.5); 4.051 (0.5); 2.871 (1.3); 2.862 (1.9); 2.853 (2.5); 2.844 (2.5); 2.835 (1.9); 2.825 (1.2); 2.515 (0.5): 2.452 (2.7); 2.434 (7.4); 2.415 (7.5); 2.395 (2.8); 2.251 (0.5); 2.143 (127.4); 2.113 (3.7); 2.092 (29.0); 1.971 (7.1); 1.952 (73.0); 1.945 (111.8); 1.943 ); 1.940 (130.1); 1.937 (90.9); 1.934 (90.5); 1.928 (48.4); 1.774 (0.5); 1.758 (0.7); 1.437 (3.1); 1.221 (0.7); 1.204 (1.2): 1.185 (0.5); 1.082 (8.3); 1.053 (15.0); 1.044 (7.9); 0.794 (1.7); 0.780 (5.1); 0.777 (5.2); 0.754 (5.5); 0.747 (2.1); 0.725 (0.4); 0.510 (2.4); 0.500 (5.7); 0.592 (7.0); 0.572 (1.7); 0.535 (0.4); 0.528 (0.3): 0.524 (0.3); 0.147 (1.4); 0.000 ); 0.149 (1.3) Example I-T3-45: 1H—NMR (400.0 MHz. CDSCN): : 8.125 (9.0); 8.092 (9.4); 7.735 (4.9); 7.730 (5.5); 7.710 (3.2); 7.705 (2.4); 7.689 (3.5); 7.584 (3.1); 7.549 (5.9); 7.542 (5.8); 7.513 (5.5); 7.492 (4.5); 7.422 (1.5); 4.140 (1.2); 4.123 (1.5); 4.115 (3.7); 4.100 (3.9); 4.093 (4.1); 4.075 (3.7); 4.059 (1.5); 4.052 (1.2); 3.545 (1.5); 2.454 (1.4); 2.455 (2.7); 2.435 (5.7); 2.417 (5.9); 2.398 (2.4); 2.378 (0.9); 2.253 (0.5); 2.221 (1.4); 2.175 (359.0); 2.125 (0.5); 2.120 (0.7); 2.114 (1.0); 2.108 (1.5); 2.094 (27.0); 1.953 (71.9); 1.947 (129.9); 1.941 (173.4); 1.935 ); 1.928 (57.7); 1.781 (0.4); 1.775 (0.7); 1.759 (1.1); 1.753 (0.7); 1.757 (0.4); 1.435 (9.9); 1.259 (0.4); 1.102 (0.5); 1.084 (8.0); 1.055 (15.0); 1.045 (7.7); 1.025 (0.5); 0.145 (2.0); 0.000 ); 0.150 (2.0) Example I-T3-46: 1H-NMR (400.0 MHz. CDSCN): 8: 8.127 (4.1); 8.085 (4.4); 7.738 (2.5); 7.732 (3.1); 7.702 (1.6); 7.697 (1.2); 7.681 (1.8); 7.676 (1.5); 7.625 (0.9); 7.551 (2.4); 7.543 (2.3); 7.495 (2.9); 7.474 (2.3); 2.453 (1.1); 2.435 (3.1); 2.416 (3.2); 2.397 (1.1); 2.158 (61.0); 2.114 (0.4); 2.108 (0.5); 2.092 (12.6); 1.964 (2.0); 1.958 (4.9); 1.953 (25.4); 1.946 ; 1.940 (61.1); 1.934 (42.3); 1.928 (21.8); 1.769 (0.4); 1.598 (1.2); 1.583 (3.1); 1.576 (3.1); 1.563 (1.6); 1.437 (16.0); 1.358 (1.6); 1.345 (3.1); 1.338 (3.2); 1.323 (1.3); 1.269 (1.8); 1.083 (4.2); 1.064 (8.8); 1.045 (4.0); 0.146 (0.7); 0.017 (0.4); 0.008 (5.9); 0.000 (150.8); 0.009 (6.1); 0.150 (0.7) Example l-T3-47: 1H-NMR (400.0 MHz. CD3CN): 8: 8.128 (3.5); 8.084 (3.8); 7.721 (2.0); 7.715 (2.5); 7.578 (1.2); 7.573 (1.0); 7.557 (1.4); 7.552 (1.2); 7.551 (2.1); 7.544 (2.1); 7.485 (2.4); 7.454 (2.2); 5.338 (0.5); 5.315 (1.1); 5.295 (1.1); 5.275 (0.5); 3.544 (1.4); 3.520 (2.8); 3.498 (1.8); 3.370 (1.7); 3.349 (2.5); 3.345 (2.4); 3.325 (1.4); 2.455 (0.9); 2.437 (2.5); 2.418 (2.7); 2.399 (0.9); 2.155 (9.4); 2.153 (19.8); 2.107 (0.4); 2.095 (10.7); 1.954 (1.2); 1.958 (3.1); 1.952 (15.2); 1.945 (27.1); 1.940 (35.2); 1.934 (25.2); 1.928 (13.1); 1.437 (15.0); 1.085 (3.2); 1.055 (5.7); 1.047 (3.1); 0.145 (0.4); 0.008 (3.9); 0.000 (85.8); 0.008 (4.3); 0.150 (0.5) Example I-T3-48: 1H-NMR (400.0 MHz. CD3CN) 8: 8.251 ; 8.205 (0.8); 8.193 (15.0); 7.592 (9.7); 7.585 (12.3); 7.575 (1.0); 7.557 (5.5); 7.552 (4.9); 7.537 (9.5); 7.530 (13.3); 7.508 (11.0); 7.475 (11.5); 7.455 (9.1); 5.940 (2.5); 3.911 (0.5); 2.882 (0.7); 2.872 (2.0); 2.853 (2.8); 2.854 (4.4); 2.845 (4.3); 2.835 (2.9); 2.827 (2.0); 2.817 (0.7); 2.457 (0.3); 2.453 (0.4); 2.153 (117.4); 2.120 (0.3); 2.114 (0.5); 2.108 (0.7); 2.102 (0.5); 1.972 (1.7); 1.955 (3.3); 1.959 (8.5); 1.953 (43.3); 1.947 (77.5): 1.941 (103.5); 1.934 (71.4); 1.928 (35.7); 1.775 (0.4); 1.759 (0.5); 1.753 (0.4); 1.437 (2.0); 1.259 (0.7); 1.221 (0.4); 1.204 (0.7); 1.185 (0.3); 0.795 (2.4); 0.783 (7.5); 0.778 (9.7); 0.755 (10.2); 0.750 (7.3); 0.748 (3.3); 0.725 (0.4); 0.708 (0.4): 0.554 (0.4); 0.544 (0.4); 0.514 (3.3); 0.504 (8.5); 0.597 (9.0); 0.593 (7.8); 0.588 (7.7); 0.575 (2.3); 0.514 (0.4); 0.145 (1 3. ); 0.025 ( 0.4); 0.008 (10.5); 0.000 (259.4); 0.009 (10.3); 0.150 (1.2) Example l-T3-49: ‘H—NMR (400.0 MHz. CD3CN): 8: 8.277 (10.6); 8.206 (16.0); 7.740 (9.1); 7.735 (12.1); 7.709 (6.2); 7.704 (4.7); 7.688 (7.6); 7.683 (7.1); 7.669 (3.6); 7.645 (1.5); 7.631 (10.9);7611 (10.7); 7.574 (0.5); 7.510 (11.0); 7.500 (0.6); 7.489 (9.0); 7.475 (0.4); 7.221 (0.4); 5.448 (8.3); 4.034 (0.0); 3.914 (1.0); 3.906 VNO 2015/067647 - 10 U.) (J1 I PCT/EPZGl4/07379S 7;) 3897105) 2489111);2484115);2480111); 224310.;4) 21751509.2);2.120112); 2.114117); 2.108120) 2.102115); 2.096' 09). 1965181) 15); 1953(1167) 19471211. 5); 1.941 1284.4); 193411978); 192811034); 1.781 10. 8); 1 775 11.3); 1759 184).18;) (13); 1.757107); 1.835104); 1.598148); 1.5841123); 1.5771123); 15.83183); 1523108) 1437 107) 1403108) 138313491121) 13421128); 1.328149); 1290108); 1.270127); 1.208113); 1190112); 0882103) 0.146(3 5);0.008 (26.;4) 0.000 (693.0); -0.008 (31.4); —0.048 (0.4); -0.150 (3.5) Example I-T3-50: 1H—NMR (400.0 MHz. CDBCN): : 8.131 (3. 8); 8. 120 (0. 3); 8. 108 (3. 8); 7.670 (2. 4); 7.664 (2. 9); 7.636 (1. 7); 7.630 ( .2); 7.615 (1.9); 7.609 (1.6); 7.462 (2.8); 7.441 (2.1); 7.320 (3. 0); 7300 (1.2); 6.909 (0.6); 4.085 (0. 5); 4. 068 (1 .4;) 4.050 (1 4); 4.032 (0. 5); 3. 901 (16. 0); 2.870 (0.5); 2.861 (0.7); 2. 852 (1. 1); 2.843 (1.1); 2.834 (0.7); 2.825 (0.5); 2.147 (64. 0); 2.114 (0.3); 2. 107 (0.4); 1.972 (6. 8); 1. 964 (3. 1); 1.958 (6.8); 1. 952 (27. 1); 1946 (46.5); 1940 (60.6); 1934 ; 1928 (20.8); 1.768 (0.3); 1.437 (1.1); 1221 (1.7); ( 2.) 1186 (1.6); 0.793 (0.6;) 0.781 (1 .;8) 0.776 (2.3), 0.763 (2.4); 0.758117); 0.746 (0.8); 0.610 (0.9); 0.599 (2.1); 0.593 (2.1); 0.589 (1. 9); 0.584 (1.8); 0.571 (0.5); 0.146 (0.7); 0.008 (9.0); 0.000 (144.6); —0.009 (5.4); -0.150 (0.7) Example 1—13—51; 1H-NMR 1400.0 MHz. 003011); 8: 8.208 10.4); 8.147 13.5); 8.120 (3.6);7.717 12.2); 7.712 (2.8); 7888 (1.;6) 7.880 11.3); 7.675 104) 7.885 (2.0);7.659 11.9); 7.654(0.6): 7.644 10.5); 7.830105); 7.810103); 7.503 10.4); 7.495 12.8); 7482 103) 7.474 12.1); 7.321 12.8);73702111);408810.9);4050109); 180); 2.170 180.8); 2.114104); 2.108 10.5); 2.102103); 1.972141); 1.965 12.3);1 959 15.7); 1.9531311); 1.9471580) 1.940 174.9);1.9341510);1.928125.9); 1.775103); 1.769(0.4);1.595(1.1); 1.581 12.7); 1.574127).1580115); 1437110); 1359115) 1.348 12.7); 1.339128); 1.324111); 1.222111); 1.204121); 1.186(1.0); 1.140105); 1.13210.8;0) 281 .;8) 0.921 108) 0.148 (0.8;) 0008 17.0); 0.000 (187.7); 0.009 (6.3); 0.150 10.8) Example 1-13—52; 1H—NMR 1400.0 MHz. CD3CN): 8: 8.276 18.4); 8.183 10.3); 8.151 18.8); 8.149 17.0); 8.128 13.5); 8.104118); 8.082 (1.8); 7.883 12.9); 7.842 12.4); 7.8941. 0); 7889 151) 7.880 10.5); 7.660 13.0); 7.854122); 7.839133); 7.633 12.8); 7.474 14.9); 7.454 13.9); 8.935 11.1);4088 10.7); 10); 4.;050121) 4.032 10.7); 2.873(08); 2.863 11.2); 2.855118); 2.845 11.9); 2.838112); 2.827 10.9); 2.165(66.0);2.163(75.8); 1972 19. 5); 1.98511.3) 1959130); 1.9531189); 1.9471305); 1.941 141.0); 1.935 128.3); 145); 1.4381180); 1.289105); 1.221 12.5) 1204 (4.8); 1.188 12.4); 0.798 11.0); 0.784 12.9); 0.778 13.9); 0.788 14.1); 0.761 13.0); 0.748 11.4); 0.813 11.4); 0.802 13.5); 0.598 13.5); 0 592 13.2); 0.587 13.2); 0.574110); 0.008(21); 0.0001829); 0.009123) Example I-T3-53: 1H-NMR (400.0 MHz. : 8: 8.291 (3.8); 8.162 (4.2); 8.130 (2.0); 8.108 (0.9); 8.086 (1.0); 7.866 (1.8); 7.844 (1.5); 7.742 (2.5); 7.736 (3.2); 7.709 (2.0); 7.703 (1.5): 7.688 (2.7); 7.682 (2.4); 7.506 (3.0); 7.485 (2.4); 2.196 (8.5); 2.183 (24.4); 1.972 (1.1); 1.965 (0.6); 1.959 (1.4); 1.954 (7.8); 1.947 (14.2); 1.941 (19.1); 1.935 (13.1); 1.929 (6.7); 1.599 (1.3); 1.585 (3.1); 1.578 (3.1); 1.564 (1.7); 1.436 (16.0); 1.362 (1.7); 1.349 (3.0); 1.342 (3.1); 1.327 (1.3); 1.204 (0.6); 0.008 (1.6); 0.000 (44.8); —0.009 (1.6) Example I-T3-54: 'H-NMR (400.0 MHz. CD3CN): 8: 8.162 (0.9); 8.153 (15.7); 8.108 (12.4); 7.996 (6.8); 7.952 (7.0); 7.683 (9.7); 7.678 (12.2); 7.666 (0.8); 7.650 (6.7); 7.644 (4.9); 7.829 (7.9); 7.624 (6.4); 7.513 (0.4); 7.469 (11.7); 7.448 (9.3); 6.931 (2.4); 5.448 (0.6); 4.235 (0.4); 4.218 (0.4); 4.086 (0.6); 4.068 (1.8); 4.057 (0.4); 4.050 (1.8); 4.032 (0.6); 2.879 (0.8); 2.870 (2.2); 2.860 (2.8); 2.852 (4.7); 2.842 (4.7); 2.834 (2.9); 2.824 (2.2); 2.814 (0.7); 2.473 (0.6); 2.468 (1.0); 2.463 (1.4); 2.459 (1.0); 2.454 (0.5); 2.276 (0.4); 2.264 (0.4); 2.245 (0.6); 2.226 (0.8); 2.159 (388.9); 2.116 (47.5): 2.108 (3.9); 2.101 (1 .9); 2.095 (1 .0); 2.050 (0.8); 2.035 (0.7); 2.017 (1.1); 1.998 (1.0); 1.972 (9.4); 1.964 (12.6); 1.958 (30.5); 1.953 (165.9); 1.946 (298.2); 1.940 (398.5); 1.934 (272.4); 192811390); 1.915 (1.9); 1.781 (0.9); 1.775 (1.6); 1.769 (2.3); 1.762 (1.6); 1.756 (0.8); 1.509 (0.3); 1.437 (13.5); 1.341 (0.4); 1.307 (1.0); 1.289 (1.9); 1.269 (16.0); 1.222 (2.4); 1.204 (4.5); 1.186 (2.2); 0.898 (0.7); 0.881 (2.2); 0.864 (1.0); 0.793 (2.4); 0.780 (7.3); 0.775 (9.5); 0.762 (10.1); 0.757 (6.9); 0.745 (3.2); 0.723 (0. 5); 0.705 (0.5); 0.650 (0.4); 0.640 (0.5); 0.631 (0.5): 0.626 (0.6); 0.610 (3.5); 0.600 (7.9); 0.598 (7.8); 0.593 (8.2); 0.588 (7.1); 0. 583 (7.2); 0.571 (2.4); 0.523 (0 3); 0.393 (O 5); 0.385 (0.5); 0.381 (0.5); 0.376 (0.5); 0.146 (3.4); 0.008 (28.7); 0.000 (825.5); -0.009 (28.8); -0.030 (0.5); —0.150 (3.4) Example 1—13—55; 1H-NMR 1801.8 MHz. 003011): 8: 8.188 13.1); 8.185 13.2); 8.124124); 8.000 11.2); 7.954112); 7.732120); 7.729 12.3); 7.697(1.3); 7.893111); 7.883 11.5); 7.679(1.3): .499123); 20). 2.1.80180); 81) 2175 (8.7); 2.172 19.0); 2.169 ; 2.187 (8.6); 2.183 112.2); 2.117 18.8); 1.973 10.8); 07); 1.958119) 1) 19501127) 19481222); 1.9421321); 1.938(21.1); 1.9341105); 1.591 11.0); 1.581 12.2); 1.577 12.2); 1.588 11.1); 1.4381180); 1.354112); 1.345122); 1.341 123); 1.331 110); 1.204104); 0.005 11.3); 0.000 (42.8): -0.006 (1.2) Example I—T3-56: 1H-NMR 1400.0 MHz. 003cm; 8: 8.210 (7.6); 8.194 10.9); 8.188 115.9); 160); 8.181 10.7);8.1491141);8.05917.8); 7.888 19.8); 7.881 112.3); 7.853 18.8); 7.847 .0); 7.832 17.9); 7.828 18.5); 7.517 10.3); 7.4731118); 7.452 19.1); 8.900 12.7); 2.878 10.7); 2.889121); 2.859 12.9); 2.851 (4.6); 2.841 (4.6); 2.832 12.9); 2.823 12.2); 2.813 10.7); 2.138 1419); 2.120105); 2.113 10.8); 2.107 (0.8); 2.101 10.5); 2.088104); 1.984 115.3); 1.958 19.2); 1.9521490); 1.948 188.5); 1940 (118.3); 1.934 (80 8); 1. 9271412); 1.915105); 1.774105); 1.788 10.7); 1.762 10.5); 1.270104); 1.792 12.4); 0780172) 0.775198) 07.821101) 0757 17. 0); 0.745 13 3); 0.723 104) 04) 0.650(04); 0.840 (0.4);0.610(3.3); 0.800 (8.0) 0599 (80) 0593184) 0589 174) 0584175) 0.571124); 4); 0 14810.9) 0008174) 000012183); 0.009 (7.6);- 0.150109) Example 1—13—57;1H—NMR 1400.0 MHz. ); 8: 8.211 12.2); 8.197142); 8.183 13.5); 8.080 12.1); 7.735 12.4); 7.730 13.0); 7.704 11.8); 7.899 11.1); 7.883 (1.8);7.678 11.5); 7.553112); 7.508 (2.8); 7.487 12.3); 2.133 (61.2); 2.113 (0.8); 2.107 10.9); 2.101 10.7);2095104); 1.964 14.3); 1.958 1113); 1.9521555); 1.948 199.8); 194011340) 19341934) 19271487) 1774108) 17.88108) 17.82105) 1.159811 1); 1.5.;82(30) 1575131) 1581 (1.6);1.437 1180;) 1.381 118) 1348130) 1341 131). 1.328112); 03); 0.148111); 0..;008190) 0..;00012332) 0009112.;0) 0.150110) Example l --T358:1H—NMR (400.0 MHz : 8: 8.212111); 8.198124) 8.168 12.0); 8.062 11.1); 7.732 11.4); 7.727120); 7.710111); 7.704 10.7); 7.889 (1.2);7683 110); 7.523(1.8) 7.502 11.4); 4.139104); 4.123 10.4); 4.118 11.2);4099112); 4.092 11.3); 12); 4.088 10.5); 4.052104); 2.154 12.8); 2.152130); 1.958108); 1.952132); 1.946 15.8); 1.940 17.8); 1.934153); 1.928127); 1.436 118.0);0008105); 0.0001144); 0.009 (0.5) Example I-T3-59: 1H—NMR (8018 MHz. ds-DMSO) 8: 19.976 12.1); 9.451 111.)5) 80) 8978177) 79) 8) 8502 (160) 8320 122) 791818.4). 7.9141119); 7.904 17.1); 7.900 14.5);7390 (68) 7886 158) 7..;5731103) 7) 4034118.); 4.02211. 5). 3338 (5769) 2.615(40); 2524 (56) 2.521 17.1); 2.518 18.3); 2.509 12200) 250814742);_2.5031854._0); 2.50014732L249712183123871135); 1.990 (4_)1.615144)_; 1.808 \VO MILE/067647 — 236 — (10 1); 1.802 (10.7); 1.593 (4.8); 1.398 (2.2); 1.300 (4.9); 1.291 (9.5); 1.288 (10.1); 1.277 (4.3); 1.175 (3.1); 0.095 (2.5); 0.005 (23.7); 0.0001 (538.1). 0.008 (20.4); 0.100 (2.7) e l—T3-60: 1HNMR (400.0 MHz. 00813). 8.: 8.887 (8.8); 8.885 (8.5); 8.595 (15.9 ; 8.577 (0.8); 8.173 (8.8); 8.188 (8.5); 8.114 (18.0); 7.901 (10.7); 7.898 (11.0); 7.587 (5.3); 7.581 (5.3); 7.555 (1.2); 7.548 (7.0); 7.540 (8.9); 7.483 (0.4); 7.428 (11.9); 7.408 (8.9); 7.284 (25.7); 8.415 (3.4); 5.301 (12.8); 2.991 ( ); 2.982 (1.7); 2.973 (3.0); 2.984 (4.1); 2.955 (4.1); 2.948 (3.1); 2.937 (1.8); 2.928 (0.7); 1.801 (5.8); 1.378 (1.1); 1.333 (0.8); 1.327 ( . (1.1); 1.255 (5.4); 0.938 (2.5); 0.921 (10. ); 0.907 (9.8); 0.903 (8.2); 0.890 (3.5); 0.880 (1.2); 0.888 (0.9); 0.882 (0 .7); 0.850 (0 9); 0.838 (0.8); 0.742 (0.4); 0.733 (0.4); 0.703 (3.0); 0.889 (8.1); 0.885 (8.5); 0.880 (8.2); 0.878 (7.9); 0.882 (2.4); 0.557 ( O.5); 0.551 ( A0.8); 0.000 (19.7); 0.008 (1.0) Example I-T3-61: ‘H-NMR (400.0 MHz. CDSCN): 8: 8.288 (8.2); 8.208 (0.5); 8.195 (8.9); 7.892 (5.7); 7.887 (8.8); 7.878 (0.7); 7.858 (3.7); 7.852 (2.8); 7.837 (4.3); 7.832 (3.5); 7.593 (5.8); 7.572 (5.8); 7.475 (8.2); 7.454 (4.9); 8.982 (1.7); 5.449 (0.9); 4.088 (0.3); 4.088 (1.1); 4.050 (1.1); 4.032 (0.4); 2.882 (0.4); 2.873 (1.2); 2.883 (1.8); 2.855 (2.5); 2.845 (2.8); 2.837 (1.7); 2.827 (1.2); 2.817 (0.4); 2.181 (57.5); 1.972 (4.8); 1.985 (1.5); 1.959 (3.8); 1.953 (18.3); 1.947 (29.0); 1.941 (37.9); 1.935 (28.4); 1.929 (13.7); 1.438 ; 1.288 (0.8); 1.221 (1.3); 1.204 (2.5); 1.186 (1.2); 0.795 (1.3); 0.783 (4.5); 0.777 (5.8); 0.785 (5.9); 0.780 (4.4); 0.747 (1.8); 0.815 (1.8); 0.805 (5.0); 0.803 (5.0); 0.598 (5.5); 0.593 (4.9); 0.588 (4.8); 0.578 (1.4); 0.000 (58.7); 0.009 (3.0) Example l-T3-62: 1H—NMR (801.8 MHz. CDBCN): 8: 8.282 (5.8); 8.209 (9.7); 7.742 (5.2); 7.738 (5.1); 7.705 (3.5); 7.702 (2.9); 7.592 (4.0); 7.888 (3.5); 7.844 (0.8); 7.594 (5.2); 7.580 (5.1); 7.508 (8.4); 7.493 (5.8); 2.197 ; 2.194 (14.8); 2.191 (18.8); 2.188 (18.2); 2.188 (18.8); 2.184 (18.2); 2.181 (15.5); 2.179 (18.7); 1.973 (1.0); 1.987 (1.1); 1.959 (2.7); 1.954 (3.0); 1.951 (18.5); 1.947 (31.7); 1.942 (48.4); 1.938 (30.9); 1.984 ; 1.594 (2.8); 1.584 (8.5); 1.580 (8.4); 1.571 (3.2); 1.544 (0.3); 1.438 (18.0); 1.359 (3.2); 1.350 (8.2); 1.345 (8.8); 1.338 (2.7); 1.288 (0.4); 1.204 (0.5); 0.005 (1.2): 0.000 (39.8); 0.008 (1.3) Example 321H-NMR (400.0 MHz. de-DMSO): 8: 8.888 (5.1); 8.523 (1.9); 8.512 (2.0); 8.389 (5.2); 7.850 (2.9); 7.814 (2.7); 7.738 (1.2); 7.730 (1.9); 7.710 (7.1); 7.511 (2.5); 7.490 (2.1); 3.327 ; 2.858 (0.5); 2.848 (0.8); 2.838 (1 .2); 2.828 (1.2); 2.819 (0.8); 2.810 (0.5); .871 (0.4); 2.508 (48.0); 2.502 ; 2.498 (48.8); 2.438 (0.8); 2.329 (0.4); 2.203 (0.8); 2.188 (12.9); 1.398 (18.0); 0.727 (0.7); 0.714 (2.3); 0.709 (3.0); 0.897 (2.8); 0.891 (2.5); 0.880 (0.9); 0.580 (0.9); 0.549 (3.0); 0.543 (3.1); 0.534 (27); 0.522 (0.7); 0.000 (42.2) Example l-T3-64: 1H—NMR (400.0 MHz. ds-DMSO): 8: 9.432 (2.1); 8.889 (2.8); 8.404 (2.9); 7.853 (1.5); 7.818 (1.5); 7.795 (0.8); 7.789 (1.2); 7.780 (1.7); 7.775 (2.8); 7.580 (1.8); 7.552 (0.4); 7.538 (1.4); 3.327 (22.2); 2.507 (17.7); 2.502 (23.3); 2.498 (17.9); 2.438 (0.3); 2.189 (8.9); 1.989 (0.4); 1.815 (0.7); 1.800 (1.8); 1.594 (1.9): 1.581 (0.8); 1.398 (18.0); 1.284 (0.8); 1.270 (1.8); 1.284 (2.0); 1.249 (0.7); 0.008 (0.7); 0.000 (19.4) Example l-T3-85: ‘H-NMR (500.1 MHz. ds-DMSO): 8: 9.728 (2.4); 8.559 (1.7); 8.558 (1 .8); 8.308 (2.2); 7.930 (0.7); 7.914 (1.5); 7.897 (0.8); 7.588 (3.9); 7.487 (1.5); 7.450 (1.4); 3.305 (13.5): 2.508 (2.9); 2.504 (8.0); 2.501 (8.2); 2.497 (5.1); 2.494 (3.0); 2.108 (18.0); 1.845 (0.8); 1.834 (2.0); 1.828 (2.1); 1.817 (0.8); 1.239 (1.1); 1.228 (2.0); 1.222 (2.1); 1.211 (0.8); 0.000 (5.4) Example l-T3-88:1H—NMR (400.2 MHz. de-DMSO): 8: 9.728 (4.5); 8.587 (3.8); 8.583 (3.8); 8.305 (4.5); 7.934 (1.5); 7.913 (3.1); 7.892 (1.7); 7.597 (3.1); 7.582 (3.1); 7.488 (3.1); 7.447 (2.9); .753 (0.4); 3.427 (0.5); 3.807 (130.4); 3.283 (0.9); 3.235 (0.8); 2.859 (0.5); 2.504 (81.2); 2.500 (82.9); 2.498 (81.8); 2.431 (1.1); 2.41 (3.4); 2.394 (3.5); 2.375 (1.2); 2.327 (0.5); 2.322 (0.4); 2.087 (18.0); 1.987 (0.8); 1.848 (1.8); 1.834 (4.0); 1.828 (4.2); 1.814 (1.7); 1.483 (0.4); 1.240 (2.1); 1.227 (4.0); 1.220 (4.2); 1.208 (1.5); 1.174 (0.4); 1.031 (5.0); 1.012 (10.8); 0.993 (4.8); 0.148 (0.8); 0.008 (5.8); 0.000 A128.9); 0.150 (0.5) Example I-T3-67: 1H-NMR (400.0 MHz. dp-DMSO): 8: 8.778 (1.2); 8.757 (1.2); 8.544 (1.7); 8.539 (1.8); 8.297 (2.1); 7.878 (0.8); 7.855 (1 .5); 7.834 (0.8); 7.593 (3.9); 7.418 (1 .5); 7.397 (1.4); 3.903 (3.9); 3.331 (120.3); 2.855 (0.5); 2.848 (0.7); 2.838 (0.7); 2.827 (0.5); 2.818 (0.3); 2.878 (0.5); 2.871 (0.7); 2.887 (0.8); 2.524 (2.0): 2.511 (45.1); 2.507 ; 2.502 (113.1); 2.498 (83.2); 2.333 (0.5); 2.329 (0.7); 2.324 (0.5); 2.120 (0.9); 2.105 (18.0); 0.752 (0.4); 0.739 (1.3); 0.734 (1.7); 0.721 (1.7); 0.718 (1.4); 0.704 (0.5); 0.522 (0.8); 0.511 (1.8); 0.505 (1 .8); 0.501 (1.5); 0.498 (1.5); 0.483 (0.5); 0.000 (6-3) Example I-T3-68: 1H—NMR (500.1 MHz. ds-DMSO); 8: 8.752 (2.4); 8.743 (2.4); 8.581 (3.4); 8.558 (3.7); 8.289 (4.4); 7.888 (1 .5); 7.851 (3.0); 7.834 (1.8); 7.597 (3.0); 7.583 (3.0); 7.411 (3.0); 7.394 (2.9); 3.304 (38.0); 2.881 (0 8); 2.854 (0.9); 2.847 (1 .4); 2.839 (1.4); 2.831 (0.9); 2.824 (0.7); 2.507 (5.9); 2.504 (14.1); 2.500 (19.4): 2.497 (14.5); 2.493 (7.2); 2.428 (1 2); 2.411 (3.5); 2.398 (3.8); 2.381 (1.2); 2.101 (1.1); 2.089 (16.0); 1.029 (5.5); 1.013 (11.1); 0.998 (5.0); 0.748 (0.9); 0.738 (2.7); 0.732 (3.5); 0.722 (3.4); 0.718 (2.8); 0.708 (1.0); 0.521 (1.1); 0.512 (3.3); 0.508 (3.3); 0.505 (3.1); 0.500 (3.1); 0.490 (0.9); 0.008 (0.7); 0.000 (14.7); 0.007 (0.8) Example I-T3—69: 1H-NMR (400.2 MHz. O): 8: 9.352 (4.3); 8.553 (4.2); 8.288 (4.4); 7.955 (1.0); 7.948 (2.0); 7.927 (1.1 ); 7.801 (3.3); 7.587 (3.5); 7.478 (0.9); 7.480 (2.0); 7.444 (1.3); 7.350 (2.0); 7.331 (3.4); 7.312 (1.5); 3.342 (0.4); 3.308 (118.1); 3.290 (0.6); 2.889 (0.3); 2.504 ; 2.500 (55.9); 2.498 (39.1); 2.443 (1.2); 2.425 (3.8); 2.408 (3.8); 2.387 (1.2); 2.327 (0.3); 2.097 (18.0); 1.595 (1 .7); 1.581 (4.8); 1.574 (4.3); 1.581 (1.8); 1.293 (2.0); 1.279 (4.8); 1.273 (4.3); 1.258 (1 .8); 1.238 (0.8); 1.041 (4.9); 1.022 (10.0); 1.003 (4.8); 0.000 (32.0); -0.008 (1.3) Example I-T3—70: 1H—NMR (400.2 MHz. de-DMSO): 8: 8.528 (3.4); 8.524 (3.8); 8.458 (1.7); 8.445 (1.7); 8.270 (4.0); 7.898 (0.9); 7.891 (0.9); 7.877 (1.7); 7.873 (1.8): 7.858 (1.0); 7.854 (0.9); 7.598 (2.8); 7.585 (2.8); 7.403 (0.8); 7.399 (0.8); 7.384 (1.7); 7.388 (1.2); 7.384 (1.1); 7.303 (2.5); 7.284 (3.9); 7.285 (1.7); 3.309 (77.4); 2.875 (0.8); 2.888 (0.8); 2.857 (1.3); 2.847 (1.4); 2.839 (0.8); 2.829 (0.8); 2.509 (11.1); 2.505 (23.7); 2.500 (33.3); 2.498 (24.8); 2.491 (11.5); 2.442 (1.1); 2.423 (3.4); 2.404 (3.5); 2.388 (1.2); 2.098 ; 1.238 (0.8); 1.040 (5.1); 1.021 (11.2); 1.002 (5.0); 0.725 (0.9); 0.712 (2.5); 0.707 (3.5); 0.895 (3.3); 0.889 (2.7); 0.877 (1.2); 0.557 (1.2); 0.548 (3.4); 0.540 (3.0); 0.538 (2.8); 0.530 (2.8); 0.518 (0.9); 0.008 fi0.7); 0.000 (21.2); 0.009 (0.8) Example 171; 'H-NMR (400.0 MHz. CDBCN): 8:: 8.180 (3.8); 8.139 (3.7); 7.784 (2.0); 7.739 (2.0); 7.733 (2.7); 7.704 (1.3); 7.899 (1.2); 7.883 (3.4); 7.878 (23); 7.553112); 7.502 (2.4); "’0 2015/067647 - ix.) U) \I 1 7.481 (1 9). 3.080 (0 5). 2.851 (0.5); 2.520 (0 812.501 (2.5); 2 482 (2.5); 2.483 (0.9); 2134 (30.8); 2.114 (0.4); 2.107 (0.5); 2.101 (0.4); 1.984 (2.0); 1.958 (4.9); 1.952 (28.1); 1.946 (52.7); 1.940 (72.6); 1.934 (52.8); 1.928 (28.4); 1.768 (0.4); 1.762 (0.3); 1.598 (1.0); 1.583 (2.5), 1.577 (2.7). 1.563 (1.4), 1.4371160), 1.381 (1 3); 1.347 (27); 1.340 (2.9); 1.328 (1 1); 1.102 (3.5). 1.083 (7.4); 1.084 (3.4); 0.1411 (0.4); 0.008 (3.1); 0.000 (97.3); 0.150 (0.4) Example 172: 1H-NMR (400.0 MHz. CD3CN): : 8.150 (5.4); 8.130 (5.8); 7.764 (2.7); 7.889 (4.2); 7.884 (8.5); 7.855 (1.9); 7.850 (1.5); 7.834 (2.2); 7.829 (1.9); 7.489 (3.8); 7.448 (2.9); 8.939 (0.9); 2.871 (0.6); 2.882 (0.9); 2.853 (1.4); 2.843 (1.4); 2.834 (1.0); 2.825 (0.8); 2.518 (1.2); 2.499 (3.7); 2.480 (3.8); 2.482 (1.4); 2.188 (77.5); 2.114 (0.3); 2.108 (0.4); 1.985 (1.9); 1.959 (4.8); 1.953 (25.8); 1.947 (47.0); 1.941 (83.4); 1.935 (44.8); 1.929 (23.7); 1.789 (0.4); 1.437 (18.0); 1.100 (5.0); 1.081 (10.2); 1.082 (4.8); 0.794 (0.8); 0.781 (2.3); 0.778 (3.1); 0.783 (3.2); 0.758 (2.4); 0.748 (1.1); 0.811 (1.0); 0.800 (2.8); 0.594 (2.9); 0.590 (2.8); 0.585 (2.8); 0.572 (0.8); 0.148 (0.3); 0.008 (2.6); 0.000 (89.9); -0.008 (4.3); 0.149 (0.3) Example 1—13-73: ‘H-NMR (400.1 MHz. ds-DMSO): (p 8.77 (0.0325); 8.78 (0.0329); 8.87 (0.0447); 8.40 (0.0688); 8.07 (0.1396); 7.89 (0.0039); 7.88 (0.0202); 7.87 (0.0405); 7.43 (0.0408); 7.42 3); 3.78 (0.0029); 3.59 (0.0071); 3.30 (1.0000); 3.17 4); 3.18 (0.0042); 2.85 (0.0123); 2.84 7); 2.83 (0.0088); 2.64 0.0025); 2.50 (0.4120); 2.37 (0.0018); 1.24 (0.0054); 0.73 (0.0482); 0.72 (0.0487); 0.71 (0.0149); 0.52 (0.0154); 0.50 (0.0420); 0.49 0.01@012 2); 0.00 (0.2888); 0.12 (0.0012) Example 174: 1H-NMR (400.0 MHz. 08.011180): 8: 9.381 (5.5); 8.853 (5.5); 8.317 (0.7); 8.293 (5.8); 7.988 (1.2); 7.984 (1.3); 7.989 (2.4); 7.985 (2.4); 7.950 (1.4); 7.948 (1.3); 7.747 (4.4); 7.734 (1.5); 7.713 (7.2); 7.708 (4.3); 7.883 (0.7); 7.493 (1.1); 7.489 (1.2); 7.474 (2.5); 7.458 (1.8); 7.454 (1.5); 7.382 (3.0); 7.343 (5.1); 7.324 (2.2); 3.903 (11.7); 3.333 (284.8); 3.287 (0.3); 3.174 (0.8); 3.182 (0.8); 2.802 (1.7); 2.783 (5.4); 2.785 (5.5); 2.746 (1.8); 2.878 (1.4); .872 (1.9); 2.887 (1.4); 2.542 (1.1); 2.525 (5.8); 2.511 (121.2); 2.507 (238.9); 2.503 (309.3); 2.498 (228.5); 2.494 (115.5); 2.334 (1.3); .329 (1.8); 2.325 (1.4); 1.803 (2.2); 1.589 (5.6); 1.582 (8.0); 1.589 (2.8); 1.298 (2.8); 1.285 (5.7); 1.278 (8.1); 1.284 (2.3); 1.237 (0.5); 1.060 (7.3); 1.042 (18.0); 1.023 (7.2); 0.008 (0.6); 0.000 (17.8); -0.008 (0.7) Example l-T3-75: 1H-NMR (400.2 MHz. de—DMSO): 8: 8.821 (4.9); 8.818 (5.3); 8.483 (2.4); 8.452 (2.4); 8.277 (5.0); 8.274 (5.4); 7.913 (1.3); 7.909 (1.4); 7.894 (2.4); 7.890 (2.5); 7.875 (1.4); 7.871 (1.3); 7.742 (4.3); 7.730 (1.5); 7.709 (7.2); 7.702 (4.2); 7.879 (0.7); 7.418 (1.1); 7.412 (1.2); 7.397 (2.4); 7.381 (1.7); 7.377 (1.8); 7.313 (3.4); 7.294 (5.4); 7.275 (2.3); 3.333 (0.8); 3.324 (0.5); 3.307 (125.1); 3.285 (0.5); 2.879 (0.8); 2.870 (1.2); 2.881 (1.9); 2.851 (1.9); 2.842 (1.2); 2.833 (0.9); 2.822 (0.4); 2.798 (1.7); 2.780 (5.3); 2.781 (5.5); 2.742 (1.8); 2.509 (17.8); 2 505 (38.4); 2.500 (54.1); 2.496 (39.8); 2.491 (19.1); 2.327 (0.3); 1.235 (0.5); 1.081 (7.3); 1.042 (16.0); 1.023 (7.1); 0.729 (1.2); 0.718 (3.4); 0.711 (4.8); 0.899 (4.5); 0.893 (3.7); 0.882 (1.8); 0.562 (1 .8); 0.552 (4.7); 0.548 (4.2); 0.542 (4.0); 0.538 (3.9); 0.524 (1.2); 0.008 (1.4); 0.000 (45.5); 0.009 (1.9) e l-T3-76: ‘H-NMR (400.1 MHz. (15.011180); 8: 9.531 (3.2); 9.102 (3.2); 9.098 (3.3); 8.822 (3.2); 8.817 (3.3); 8.727 (5.1); 8.442 (1.9); 8.438 (3.4); 8.428 (5.4); 7.817 (2.1); 7.582 (2.1); .759 (16.0); 3.588 (2.8); 3.437 (0.3); 3.424 (0.4); 3.328 (355.3); 3.303 (1.2); 2.711 (0.5); 2.875 (0.8); 2.670 (0.7); 2.887 (0.5); 2.557 (0.4); 2.554 (0.7); 2.552 (0.9); 2.551 (1.1); 2.541 ); 2.530 (1.2); 2.528 (1.0); 2.527 (1.0); 2.524 (1.3); 2.510 (33.8); 2.508 (87.9); 2.502 (90.5); 2.497 (83.3); 2.493 (29.5); 2.458 (0.9); 2.440 (2.5); 2.421 (2.5); 2.402 (0.9); 2.388 (0.5); 2.333 (0.6); 2.329 (0.7); 2.324 (0.8); 2.111 (12.0); 2.088 (1.1); 1.829 (1.2); .815 (2.9); 1.808 (3.2); 1.595 (1.5); 1.348 (1.4); 1.332 (2.9); 1.325 (3.2); 1.311 (1.1); 1.072 (0.8); 1.055 (1.3); 1.048 (4.1); 1.037 (0.9); 1 .029 (8.8); 1.010 (3.8); 0.008 (2.0); 0.000 (88.8); 0.008 (2.4); 0.014 (0.4) e 1—13-77: 1H—NMR (400.1 MHz. O)I 8: 9.043 (4.2); 9.038 (4.3); 8.798 (4.2); 8.793 (4.4); 8.705 (6.6); 8.845 (1.9); 8.835 (2.0); 8.409 (8.8); 8.389 (2.6); 8.384 (4.8); 8.379 (2.8); 7.813 (2.8); 7.580 (2.9); 5.759 (4.7); 3.327 (158.8); 2.902 (0.8); 2.892 (1.0); 2.884 (1.5); 2.874 (1.5); 2.866 (1.0); 2.858 (0.7); 2.871 (0.4); 2.541 (85.9); 2.511 (20.9); 2.508 (42.9); 2.502 (59.0); 2.498 (43.4); 2.493 (22.4); 2.458 (2.1); 2.438 (3.5); 2.419 (3.4); 2.401 (1.3); 2.387 (0.3); 2.329 (0.4); 2.110 (18.0); 2.086 (1.2); 1.989 (0.4); 1.072 (0.4); 1.055 (1.0); 1.048 (5.3); 1.029 (11.8); 1.010 (5.3); 0.783 (0.9); 0.750 (2.3); 0.745 (3.4); 0.733 (3.3); 0.727 (2.8); 0.718 (1.4); 0.817 (1.2); 0.807 (3.5); 0.800 (3.1); 0.591 (2.8); 0.579 (1.0); 0.008 (1.3); 0.000 (40.7); —0.008 (2.2) Example l—T3-78: 1H-NMR (400.1 MHz. 416-00180): 8: 9.542 (5.5); 9.127 (5.7); 9.122 (5.9); 8.857 (8.8); 8.834 (5.8); 8.829 (5.9); 8.472 (3.3); 8.487 (5.7); 8.481 (3.2); 8.434 (8.9); 7.757 (4.0); 7.724 (7.7); 7.899 (0.8); 5.759 (5.9); 4.020 (0.4); 3.811 (0.8); 3.588 (1.5); 3.428 (0.9); 3.328 (384.4); 3.303 (1.4); 3.235 (1.3); 2.821 (1.8); 2.802 (5.1); 2.783 (5.1); 2.765 (1.7); 2.711 (0.6); 2.870 (0.9); 2.888 (0.7); 2.541 (184.7); 2.510 ; 2.508 (100.5); 2.502 (137.3); 2.497 98.8); 2.493 (47.9); 2.387 (0.8); 2.329 (0.8); 1.989 (1.5); 1.833 (2.1); 1.819 (5.2); 1.812 (5.6); 1.599 (2.4); 1.350 (2.6); 1.337 (5.3); 1.330 .5); 1.318 (2.0); 1.234 (0.4); 1.192 (0.4); 1.174 (0.8); 1.158 (0.5); 1.148 (0.5); 1.089 (7.2); 1.050 (18.0); 1.032 (7.1); 0.146 (0.4); 0.008 2.9); 0.000 (90.5); 0.008 (3.5) Example l-T3-79: 1H-NMR (500.1 MHz. d8-DMSO): 8: 9.064 (5.0); 9.059 (5.1); 8.821 (8.9); 8.811 (5.2); 8.807 (5.3); 8.630 (2.5); 8.622 (2.5); 8.413 (3.8); 8.408 (13.3); 7.748 (4.3); 7.738 (1.8); 7.721 (6.6); 7.712 (3.8); 7.695 (0.9); 5.752 (1.0); 3.305 (76.3); 3.281 (0.4); 2.910 (0.4); 2.902 (0.9); 2.895 (1.3); 2.888 (2.0); 2.880 (2.0); 2.873 (1 .3); 2.865 (1.0); 2.858 (0.4); 2.813 (1 .7); 2.798 (5.5); 2.783 (5.6); 2.768 (1.9); 2.508 ; 2.504 ; 2.501 (39.3); 2.497 (29.3): 2.494 (14.5); 1.908 (2.7); 1.236 (0.5); 1.068 (7.4); 1.053 (16.0); 1.038 (7.3); 0.761 (1.2); 0.751 (3.5); 0.747 (4.8); 0.737 (4.6); 0.733 (3.8): 0.723 (1.6); 0.620 (1.6); 0.612 (4.7); 0.607 (4.4); 0.604 (4.2); 0.599 (4.0); 0.589 (1.2); 0.006 (1 .3); 0.000 (30.6); —0.007 (1.4) Example l-T3-80: 1H-NMR (400.0 MHz. CDBCN): 8: 8.128 (2.6); 8.082 (2.8); 7.736 (1.6); 7.731 (2.1); 7.701 (1.1); 7.696 (0.8); 7.680 (1.2); 7.675 (1.1); 7.608 (0.4); 7.562 (1.4); 7.549 (1.4); 7.494 (1.9); 7.473 (1.5); 2.448 (0.6); 2.429 (1.9); 2.410 (2.0); 2.391 (0.7); 2.164 (9.8); 2.155 (20.2); 2.088 (7.6); 1.965 (1.0); 1.959 (2.5); 1.953 (13.9); 1.946 (25.4); 1.940 (34.2); 1.934 (24.1); 1.928 ; 1.598 (0.8); 1.583 (2.0): 1.577 (2.0); 1.563 (1.1); 1.437 (16.0); 1.358 (1.0); 1.345 (2.0); 1.338 (2.1); 1.323 (0.8); 1.268 (0.7); 1.092 (2.7); 1.073 (5.7): 1.054 (2.6); 0.008 (1.1); 0.000 (34.6); 0.009 (1.5) Example l-T3—81: 1H-NMR (400.0 MHz. CD3CN): 8: 8.115 (7.2); 8.067 (7.4); 7.688 (4.4); 7.683 (5.6); 7.667 (0.5); 7.652 (3.0); 7.646 (2.4); 7.631 (3.5); 7.625 (3.0); 7.560 (4.1); 7.546 (4.1): 7.462 (5.2); 7.441 (4.2); 6.903 (1.2); 2.880 (0.3); 2.871 (0.9); 2.861 (1.3); 2.853 (2.1); 2.843 (2.1); 2.835 (1.3); 2.825 (1.0): 2.815 (0.4); 2.447 (1.8); 2.428 (5.5); 2.409 (5.7); 2.390 (1.9); 2.141 ; 2.120 (1.0); 2.113 (0.9); 2.107 (1.0); 2.101 (0.9); 2.086 (21.5); 1.964 (4.2); 1.958 (10.5); 1.952 (54.5); 1.946 (98.5); 1.940 (132.1); 1.934 (92.1); 1.927 (48.4); 1.774 (0.5); 1.768 (0.8); 1.762 (0.5); 1.437 (1.3); 1.270 (1.0), 1.090 (7.7); 1.071 (16.0); 1.052 (7.4); 0.794 (1.1); 0.781 (3.3); 0.776 (4.4); 0.763 (4.7); 0.758 (3.4); 0.746 (1.6); 0.610 (1.5); 0.598 (3.8); 0.592 (4.0); 0.588 (3.6); 0.583 (3.6); 0.571 (1.1); 0.146 (18); 0.031 (0.4); 0.030 (0.4);700272 (0.4); 0.0265 (0.4); 0.026 (0.4);0022 ‘NO 2015/067647 — 238 — (0.8): 0.008 (18.0); 0.000 (381.4); 0.009 (18.8); 0 150 (1.8) Example l-T3-82: 'H-NMR (400.0 MHz. 003011)- 8= 8.127 (7.5); 8.085 (7 7); 7.734143); 7 729 (5.7); 7.708 13.2); 7 703 (2.2). 7.888 (3.8); 7 882 (2.9); 7.581 (3.9). 7.548 (3.8); 7.512 (5.3). 7.491 (4.4); 7.385 (0.9); 4.141 (1.1); 4.124 (1.2); 4.117 (3.5); 4.100 (3.5), 4.093 (3.7); 4.077 (3.5); 4.070 (1.3); 4.053 (1.2); 2.482 (0.4); 2.457 (0.4); 2.450 (1.8); 2.431 (5.5); 2.412 (5.7); 2.393 (1.9); 2.150 (78.9); 2.120 (0.5); 2.113 (0.7); 2.107 (0.8); 2.101 (0.8); 2.090 ; 1.984 (3.5); 1.958 (8.4); 1.952 (45.7); 1.948 ; 1.940 (111.8); 1.934 (77.5); 1.927 (40.4); 1.774 (0.4); 1.788 (0.8); 1.782 (0.4); 1.437 (1.0);1.269(1.0); 1.093 (7.7); 1.074 (18.0); 1.055 (7.4); 0.148 (1.4); 0.008 (11.1); 0.000 (291.0); 0.009 (12.7); 0.150 (1.4) Example l-T3-83: 1H-NMR (400.0 MHz. CDSCN): 8: 8.128 (7.9); 8.079 (8.4); 7.719 (4.9); 7.713 (8.1); 7.877 (3.1); 7.871 (2.5); 7.858 (3.5); 7.850 (3.1); 7.582 (4.8); 7.548 (4.7); 7.484 (5.8); 7.483 (5.1); 7.438 (1.2); 5.447 (1.2); 5.337 (1.3); 5.318 (2.5); 5.295 (2.5); 5.274 (1.3); 4.088 (0.4); 4.050 (0.4); 3.543 (3.2); 3.540 (2.1); 3.520 (8.4); 3.498 (4.2); 3.370 (4.2); 3.387 (2.8); 3.350 (8.2); 3.348 (5.9); 3.328 (3.3); 2.482 (0.3); 2.451 (2.0); 2.432 (8.0); 2.413 (8.2); 2.394 (2.1); 2.150 (115.8); 2.120105); 2.114 (0.7); 2.107 (0.9); 2.091 (23.5); 1.972 (1.9); 1.984 (3.0); 1.958 (7.9); 1.952 (39.4); 1.948 (71.5); 1.940 (98.0); 1.934 (88.4); 1.928 (38.7); .774 (0.4); 1.788 (0.8); 1.782 (0.4); 1.437 (2.7); 1.288 (1.0); 1.221 (0.4); 1.204 (0.8); 1.188 (0.4); 1.094 (7.8); 1.075 (18.0); 1.058 (7.5); 0.148 (1.1); 0.008 (9.8); 0.000 (220.9); 0.150 (1.1) Example I-T3-84: 1H-NMR (400.0 MHz. CD3CN): 8: 8.182 (9.4); 8.125 (7.5); 7.997 14.3); 7.952 (4.4); 7.729 (4.8); 7.724 (8.8); 7.707 (3.5); 7.701 (2.3); 7.888 (3.9); 7.880 (3.2); 7.519 (8.1); 7.498 (4.9); 7.348 (1.3); 4.140 (1.3); 4.123 (1.4); 4.118 (3.9); 4.100 (3.9); 4.092 (4.2); 4.078 (3.9); 4.089 (1.7); 4.052 (1.4); 2.148 (92.5); 2.1201272); 2.108 (1.8); 2.101 (0.9); 2.095 (0.5); 1.971 (0.9); 1.984 (3.5); 1.958 (9.1); 1.952 (47.9); 1.948 ; 1.940 (118.0); 1.934 (83.5); 1.928 (44.7); 1.774105); 1.788 (0.7); 1.782 (0.5); 1.437 (18.0); 1.270 (0.8); 0.148 (0.9); 0.008 (8.8); 0.000 (179.6); 0.008 ;— 0.150 (0.9) Example I-T3-85: 11+vale (400.0 MHz. CD3CN): 8: 8.183 (5.2); 8.118 (4.2); 7.998 (2.5); 7.953 (2.5); 7.718 (3.0); 7.710 (3.7); 7.875 (1.9); 7.889 (1.5); 7.854 (2 .2); 7.848 (1.9); 7.490 (3.5); .489 (2.8); 7.418 (0.8); 7.400 (0.8); 5.335 (0.8); 5.314 (1.6); 5.293 (1.8); 5.272 (0.8); 3.542 (2.0); 3.538 (1. ); 3.518 (4.0); 3.498 (2.8). 3.370 (2.8); 3.387 (1.7); 3.349 (3.8); 3.348 (3.8); 3.328 (2.0); 2.133 (15.0); 2.120 (15.4); 2.101 (0.5); 1.971 (1.1); 1.984 (1.7); 1.958 (4.3 )-. 1.952 (19.7); 1.948 (35.3); 1.940 (47.2); 1.934 (33.8); 1.927 (18.1); 1.437 (16.0); 1.204 (0.4); 0.148 (0.4); 0.008 (3.9); 0.000 (78.7); 0.150 (0.4) Example I-T3-86: ‘H-NMR (400.0 MHz. 003011); 8: 8.252 (0.3); 8.148 (2.7); 8.110 (0.4); 8.102 (2.9); 7.899 (1.3); 7.708 (1.4); 7.890 (1.7); 7.885 (2.2); 7.855 (1.2); 7.849 (0.9); 7.834 (1.5); 7.828 (1.4); 7.488 (2.2); 7.447 (1.8); 8.891 (0.5); 2.871 (0.4); 2.882 (0.5); 2.853 (0.8); 2.843 (0.8); 2.835 (0.5); 2.825 (0.4); 2.415 (1.0); 2.171 (8.3); 2.132 ; 1.971 (0.5); 1.984 (1.1); 1.958 (2.8); 1.952 (13.9); 1.9481252); 1.940 (34.0); 1.933 (23.7); 1.927 (12.5); 1.437 (18.0); 1.289 (0.4); 0.794 (0.4); 0.781 (1.3); 0.778 (1.7); 0.784 (1.8); 0.758 (1.3); 0.748 (0.8); 0.811 (0.8); 0.599 (1.5); 0.593 (1.8); 0.589 (1.4); 0.584 (1.4); 0.571 (0.5); 0.008 (2.3); 0.000 (83.9); 0.009 (3.1) Example l—T3-87: 1H-NMR (400.0 MHz. 003011); 8: 8.171 (11.0); 8.170 (11.0); 8.122 (12.2); 8.120 (11.4); 7.729 (8.8); 7.724 (8.7); 7.897 (4.9); 7.891 (3.7); 7.878 (5.8); 7.870 (4.8); 7.808 (16.0); 7.804 (15.8); 7.551 (3.2); 7.500 (8.3); 7.479 (8.7); 5.448 (0.7); 4.085 (0.8); 4.088 (2.0); 4.050 (2.0); 4.032 (0.7); 3.240 (0.6); 2.132 ; 2.119 (0.5); 2.113 (0.7); 2.107 (0.9); 2.101 (0.6); 2.095 (0.3); 1.971 (9.0); 1.984140); 1.958 (10.1); 1.952 (58.8); 1.948 (103.2); 1.940 (138.8); 1.833 (95.2); 1.927 (49.0); 1.914 (0.7); 1.780 (0.3); 1.774 (0.6); 1.788 (0.8); 1.782 (0.8); 1.595 (3.8); 1.581 (8.5); 1.574 (8.5); 1.580 (4.8); 1.520 (0.5); 1.437 (11.1); 1.400 (0.8); 1.380 (4.7); 1.348 (8.8); 1.340 (8.8); 1.325 (3.8); 1.317 (0.8); 1.287 (0.4); 1.289 (1.4); 1.221 (2.5);1204147); 1.188 (2.3); 0.148 (1.8); 0.008 (14.1); 0.000 (400.9); 0.009 (15.1); 0.150 (1.8) e I-T3-88: 1H-NMR (400.0 MHz. 003011): 8: 8.180 (10.8); 8.111 (11.3); 7.881 (8.2); 7.875 (7.9); 7.847 (3.9); 7.842 (3.1); 7.827 (4.5); 7.821 (4.0); 7.805 (18.0); 7.487 (7.2); 7.447 (5.7); 8.938 (2.0); 5.448 (0.4); 4.087 (0.5); 4.049 (0.5); 2.879 (0.4); 2.889 (1.3); 2.880 (2.0); 2.851 2.8); 2.842 (2.9); 2.833 (2.0); 2.824 (1.4); 2.814 (0.5); 2.487 (1.2); 2.482 (1.7); 2.458 (1.3); 2.253 (0.8); 2.228 (0.4); 2.158 ); 2.120 (1.0); 2.113 (1.3); 2.107 (1.8); 2.101 (1.2); 2.095 (0.7); 1.971 (3.4); 1.984 (8.0); 1.958 (20.3); 1.952 (98.7); 1.948 (178.8); 1.940 (240.8); 1.934 (170.9); 1.928 (91.2); 1.781 (0.5); 1.774110); 1.788 (1.3); 1.782 (1.0); 1.758 (0.5); 1.437 (3.0); 1.289 (0.9); 1.221 (0.5); 1.203 (1.0); 1.185 (0.5); 0.792 (1.7); 0.779 (4.8); 0.774 (8.8); 0.781 (8.5); 0.758 (5.1); 0.744 (2.2); 0.810 (2.2); 0.599 (8.0); 0.592 (8.3); 0.583 (5.4); 0.571 (1.6); 0.148 (3.3); 0.007 (29.1); 0.000 ); 0.150133) Example l-T3-89: ‘H-NMR (400.0 MHz. da-DMSO): 8: 9.437 (11.1); 8.788 ; 8.387 (18.0); 8.317 (0.8); 7.988 (0.4); 7.903 (8.8); 7.897 (8.7); 7.824 (9.1); 7.810 (13.0); 7.805 (11.4); 7.802 (13.2); 7.797 (8.0); 7.791 (3.7); 7.814 (3.7); 7.810 (3. ); 7.591 (2.9); 7.588 (2.9); 7.580 (9.0); 7.551 (1.7); 7.548 (1.5); 7.537 (7.7); 3.903 (8.5); 3.332 (418.5); 3.174 (0.7); 3.182 (0.8); 2.878 (2.0); 2.871 (2.7); 2.887 (2.1); 2.541 (1.8); 2.507 (359.7); 2.502 (464.1); 2.498 (348.7); 2.333 (2.1); 2.329 (2.9); 2.325 (2.2); 1.818 (3.7); 1. 8O4 (9.3); 1.597 (9.9); 1.584 (4.2); 1.543 (0.4); 1.327 (0.4); 1.287 (4.3); 1.274 (9.4); 1.287 (9.9); 1.253 (3.8); 1.234 (1.5); 1.215 (0.5); 1. 1 8 1 (0.4); 1.177 (0.4); 0.881 (0.4); 0.853 (0.4); 0.843 (0.4); 0.834 (0.4); 0.824 (0.4); 0.813 (0.3); 0.008 (0.9); 0.000 (24.8); 0.008 (1.1) Example 1—73-90: ‘H—NMR (400.0 MHz. 003011); 8: 8.585 (0.4); 8.349 (0.8); 8.333 ; 8.123 (0.6); 8.109 (13.1); 8.098 (0.8); 7.904 (0.4); 7.881 (0.4); 7.712 (8.7); 7.889 (18.0); 7.883 (10.7); 7.872 (1.0); 7.854 (5.5); 7.848 (4.2); 7.833 (8.1); 7.827 (5.3); 7.817 (5.0); 7.811 (5.5); 7.475 (0.5); 7.487 (9.7); 7.454 (0.7); 7.448 (9.4); 7.438 (3.3); 7.422 (2.4); 7.419 (2.6); 7.418 (2.5); 8.891 (2.1); 5.448 (0.4); 3.899 (0.8); 2.881 (0.8); 2.872 (1.7); 2.882 (2.4); 2.854 (3.8); 2.844 (3.9); 2.835 (2.5); 2.828 (1.8); 2.818 (0.8); 2.132 (82.2); 2.113 (1.1); 2.107 (1.3); 2.101 (0.9); 2.095 (0.5); 1.998 (0.3); 1.971 (0.9); 1.984 (5.7); 1.958 ; 1.952 ; 1.948 (147.9); 1.940 (200.1); 1.933 (139.4); 1.927 ; 1.780(0.5);1.774(0.8); 1.768 (1.1); 1.782 (0.8); 1.758 (0.4); 1.288 (2.3); 0.881 (0.3); 0.798 (2.0); 0.783 (5.8); 0.778 (7.9); 0.785 (8.2); 0.760 (8.0); 0.748 (2.8); 0.728 (0.4); .709 (0.4); 0.853 (0.3); 0.643 (0.3); 0.813 (2.8); 0.801 (8.7); 0.595 (7.1); 0.591 (8.3); 0.588 (8.3); 0.574 (2.0); 0.148 (2.4); 0.008 (17.8): 0.000 (508.1); 0.009 (24.9); 0.150 (2.4) Example 1;1H-valR (400.0 MHz. ds-DMSO): 8: 8.837 (3.4); 8.831 (3.8); 8.747 (8.3); 8.532 (1.9); 8.521 (2.0); 8.474 (8.2); 8.100 (9.7); 7.954 (3.3); 7.949 (3.5); 4.109 (0.4); 4.095 (0.4); 3.904 (18.0); 3.335 (287.0); 3 287 (0.5); 3.243 (0.4); 3.174 (2.4); 3.182 (2.5); 2.877 (0.8); 2.888 (0.9); 2.859 (1.3); 2.849 (1.3); 2.840 (0.9); 2.831 (0.8); 2.878 (1.0); 2.871 (1.3); 2.887 (1.0); 2.507 (158.9); 2.502 (208.2); 2.498 (158.4); 2.334 (0.9); 2.329 (1.2); 2.325 (0.9); 1.258 (0.4); 1.002 11.3); 0.988 11.2); 0740,1933): 0.727 (2350122131); 0.710129); 0.704 (2.4); 0.893 (1 E; 056811)); 0.558__(3._1);fi52 \X’O 67647 — 77.39 — 2014/073795 (2.9);0548 (2 7) 0542 (2 5) 0580 (07) 0000 (18) Example 2: 1H-NMR (400. 0 MHz. ds—DMSO): 9.415 (4.9); 8.892 (4.2), 8.886 (4.4); 8.785 (7.8); 8.488 (7.8). 8.104 (11 7); 8.044 (4.2); 8.089 (4 8) 3904 (180) 8598 (0.4); 8.886 (427.9); 3.173 (1.6); 8.168( 8); 2.876 (1.4); 2.672 (17); 2667 (18) 2518(829);2.511(114.8);250 (211.5), 2.508 (268.6); 2.498 (1,987) 2884 (11); 2329 (15); 2.325(1.1); 1.818(16); 1599 (45); 1592 (48) 1579 (2.0), 1.315(2.;1) 1.801 (4.8); 1 295 (47); 1.280 (1.7) 1.2.;35(03) 0000 (21) Example 1 T-3931‘H-NMR (400.0 MHz. CD3CN): 8: 8.187 (3.1); 8.146 (8.8); 7.899 (4.8); 7.858 (1 .3); 7.848 (2. 7); 7.639 (0.5); 7.624 (1. 5); 7818 (1 0;) 7.462 (1. 9); 7.441 (1.5); 7.115 (0.7); .449 (1.2); 4.088 (0.5); 4.050 (0.5); 2.174 (33.4); 1.972 (2 4), 1.985 (0.8); 1.959(19.); 1953 (108) 1947 (186;) 1.941 (24.;9) 1.984 (18.9); 1.928 (8.7); 1.448 (9.5); 1.487 (18.0); 1.270 1 221 (0. 6); 1.204 (1 .;12) .1086( 6); 0.887 (0. 7); 0.824 (2.1); 0.820 (2.2); 0.808 (0.9); 0.673 (1 .1); 0.661 (2.4); 0.656 (2.5); 0.844 (0.8); 0.008 (0.4); 0.000 (10 8); 0.009 (0. 8) Example I-T3-94: ‘H-NMR (400.0 MHz. CD3CN): 8: 8.149 (5.3); 8.106 (4.3); 7.996 (2.3); 7.951 (2.4); 7.645 (2.3); 7.639 (5.5); 7.632 (0.8); 7.618 (2.7); 7.612 (1.8); 7.457 (3.0); 7.436 (2.4); 7.098 (1.2); 2.468 (0.4); 2.464 (0.5); 2.459 (0.4); 2.165 (184.2); 2.116 (15.3); 2.102 (0.5); 1.972 (1.1); 1.965 (3.0); 1.959 (7.6); 1.953 ); 1.947 (74.8); 1.940 (100.0); 1.934 (68.4); 1.928 (35.0); 1.775 (0.4); 1.769 (0.6); 1.763 (0.4); 1.447 (16.0); 1.437 (3.0); 1.270 (2. 2), 1.204 (0.3); 0.835 (1.1); 0.822 (3.7); 0.818 (3.8); 0.807 (1.5); 0.673 (1.8); 0.662 (4.3); 0.656 (4.3); 0.644 (1.3); 0.008 (1.2); 0.000 (38.1); -0.009 (1-4) __———_—_——_————————— Example l-T3-95: 1H-NMR (400.0 MHz. ds-DMSO): 6: 9.598 (2.8); 8.898 (2.0); 8.887 (2.0); 8.791 (8.8); 8.545 (3.3); 8.815 (0.5); 8.800 (2.2); 8.294 (2.3); 8.283 (5.7); 4.088 (0.4); 4.020 (0.4); 8.822 (38.3); 2.671 (0.6); 2.502 (88.6); 2.828 (0.8); 1.989 (1.8); 1.848 (0.8); 1.828 (2.2); 1.821 (2.3); 1.809 (0.9); 1.898 (18.0); 1.298 (1.0): 1.285 (2.2); 1.278 (2.8); 1.264 (0.8); 1.198 (0.5); 1.175 (0.9); 1.157 (0.5); 0.146 (0.4); 0.000 ; -0150 (0.4) Example l-T3-96: 1H-NMR (400.0 MHz. d6~DMSO): 8: 8.888 (2.0); 8.888 (2.0); 8.818 (8.2); 8.518 (1.0); 8.502 (1.0); 8.877 (3.3); 7.954 (1.9); 7.949 (1.9); 7.596 (8.6); 4.104 (0.8); 8.908 (10.1); 3409 (05); 8850 (3466) 8802 (05) 3.175 (18); 3.162(18); 2885 (04); 2857 (07) 2847 (07) 2888 (04); 2677 (04); 2672 (08) 2668 (04) 2526 (18); 2.512(874); 2508 (747) 2503 (973); 2499 (712) 2494 (356) 2489 (126) 2885 (04) 2880 (06) 2325 (0.5); 2.117(16.;0) 1003 (08) 0987 (06) 0739 (05) 0728 (12); 0.721 (17) 0709 (16) 0708 (18); 0692 (06) 0588 (06) 0.557 (1.7); 0.551 (1.5); 0.547 (1.4); 0.542 (1.4); 0.529 (0.4); 0.000 (0.7) e I-T3-97: ‘H-NMR (400.0 MHz. O): 8: 9.895 (2.2); 8.892 (2.0); 8.886 (2.0); 8.640 (3.3); 8.891 (8.4); 8.040 (1.9); 8.085 (1.9); 7.599 (3.7); 4.108 (0.5); 4.095 (0.5); 8.904 (10.2); 8.888 (180.8); 8.174 (2.4); 8.181 (2.4); 2.876 (0.4); 2.671 (0.6); 2.687 (0.5); 2.541 (0.4); 2.525 (18); 2.511 (396) 2507 (81 .;0) 2.502 (95.3); 2.498 (69.0); 2.493 (84.2); 2.334 (0.4);2.329 (0.6);2.324 (0.4); 2.118(180) 1..818(0 8); 1599 (1 .;9) 1592 (21) 1579 (09); 1811 (0.9); 1.297 (2.0); 1.291 (2.1); 1.278 (0.8); 1.002 (0.5); 0.987 (0.5); 0.000 (1.2) Example l-T3—98: 1H-NMR (400.0 MHz. da-DMSO): 8: 8.839 (6.0); 8.833 (6.2); 8.791 (0.5); 8.781 (9.8); 8.692 (3.1); 8.681 (3.2); 8.549 (0.5); 8.540 (9. 8;) 8.282 (16.0); 8.217 (6.2); 8.210 (6.1); .756 (1.1); 3.326 (37.2); 2.871 (0.8); 2.861 (1.2); 2.852 (1.8); 2.842 (1.9); 2.833 (1.2); 2.824 (0. 9); 2. 814 (0. 3), 2.671 (0.4); 2. 525 (0.9); 2.511 (20. 9); 2.507 (43. 3); 2. 502 (58.6); 2.498 (44.1); 2.494 (22.5); 2.329 (0.4); 1989 (0.4);11.397 (0.4); 0.757 (1.2); 0.744 (3.4); 0.739 (47;) 0.726 (4.;5) 0.721 (3.;8) 0.709 (1.5); 0.568 (1.5); 0.557 (4.5); 0.551 (4.;2) 0.548 (4.1);0.452 (3.9) 0.530 (1.2); 0.146 (0.;5) 0.008 (3.4); 0.000 (97.0); -0. 008 (.4(2) -0. 150 (0.5) Example l-T3-99: 1H-NMR (400.0 MHZ. de-DMSO): 8: 8.851 (0.6); 8. 845 (0.8); 8.840 (3.5); 8.834 (3. 6); 8.770 (6 0); 8.525 (5.8); 8.337 (3.6); 8.331 (3.5); 8283 (11.0); 8.226 (0.6); 8.220 (0. 6); 3.328 (25.7); 3.030 (16. 0); 2.798 (0 7); 2.790 (0. 8); 2. 781 (13); 2. 771 (0. 9); 2.758 (2. 9); 2.543 (55.4); 2. 525 (0. 6); 2.508 (28.1); 2.503 (37. 2); 2.499 (27.6); 0.814 (0. 3); 0.773 (0.4); 0.604 (0. 5); 0.585 (2.1); 0.576 (2. 8); 0.566 (1.0); 0543 (1. 2); 0. 532 (2. 2); 0.514 (2.0); 0.501 (0.4); 0.495 (0. 4); 0.008 (1 .0); 0.000 (28.2); —0.008 (1 0.) Example I-T3-100:1H-NMR (400.0 MHz. ds-DMSO): 6: 8.826 (5.3); 8.817 (2.9); 8.811 (2.8); 8.531 (4.2); 8.320 (2.7); 8.314 (2.7); 8.206 (0.4); 8.200 (0.4); 8.111 (7.7); 3.904 (16.0); 3.395 (0.6); .337 (288.8); 3.257 (0.4); 3.243 (0.4); 3.175 (0.9); 3.162 (1.0); 3.029 (12.3); 2.795 (0.5); 2.788 (0.6); 2.778 (1.0); 2.768 (0.8); 2.757 (2.2); 2.676 (0.8); 2.672 (1.1); 2.668 (0.8); 2.512 (73.1); 2.507 (138.1); 2.503 (175.3); 2.499 (129.8); 2.334 (0.7); 2.330 (1.0); 2.325 (0.7); 1.002 (1.0); 0.987 (1.0); 0.833 (0.4); 0.815 (0.3); 0.603 (0.4); 0.584 (1.7); 0.574 (2.2); 0.565 (0.8); 0.542 (0.9); 0.531 (1.7); 0.513 (1.5); 0.000 (1.8) Example l-T3-101:1H-NMR (400.0 MHz. de—DMSO): 8: 8.828 (0.4); 8.823 (0.4); 8.815 (2.1); 8.809 (2. 2); 8.690 (3. 8); 8.442 (0.7); 8.435 (3.3); 8.293 (2.2); 8.287 (2.1); 8.190 (0.4); 8.184 (0.3); 7.603 (4.3); 3.904 (8.8); 3.339 (233.4); 3.175 (0 6); 3.162 (0. 6); 3.027 (9.9); 2.795 (0.4); 2.787 (0.5); 2.778 (0.8); 2.768 (0.6); 2.756 (1.8); 2.676 (0.6); 2.672 (0.8); 2.667 (0.6); 2.512 (51.7), 2.507 (99.0), 2.503 (126.8); 2.498 (93.4); 2.494 (47.1); 2.334 (0.6); 2.330 (0.8); 2.325 (0.6); 2.130 (16.0); 2.122 (3.6); 1.002 (0.4); 0.987 (0.4); 0.583 (1.3); 0.574 (1.7); 0.565 (0.6); 0.543 (0.7); 0.531 (1.3); 0.514 (1.1); 0.000 (0.9) Example l-T3—102z1H-NMR (400.0 MHz. da-DMSO): 8: 8.908 (0.7); 8.879 (2.4); 8.874 (2.4); 8.833 (4.2); 8.820 (1.2); 8.538 (3.8); 8.496 (1 .0); 8.431 (0.7); 8.427 (0.7); 8.288 (2.4); 8.283 (2.4); 8.111 (9.5); 3.904 ; 3.591 (0.4); 3.341 (514.4); 3.175 (1 .0); 3.162 (1.0); 3.136 (2.9); 2.914 (11.4); 2.676 (1.1); 2.672 (1.5); 2.668 (1.1); 2.507 (189.0); 2.503 (242.9); 2.499 (186.3); 2.334 (1 .1); 2.330 (1 .5); 2.326 (1.1); 1.713 (2.7); 1.489 (2.0); 0.000 (2.0) Example I-T3-103: 1H-NMR (400.0 MHz. ds-DMSO): 8: 8.907 (04); 8.878 (1. 3); 8.872 (1. 3); 8.702 (2 2); 8685 (0.6); 8.443 (2.1); 8.406 (0.9); 8.270 (1. 3); 8264 (1.3); 7.604 (4.3); 3.904 (12.6); 3. 395 (0. 4); 3. 338 (210.6); 3.270 (0. 4); 3.256 (0. 3); 3. 175 (0.8); 3. 162 (0. 9); 3.133 (1.6); 2.915 (6. 3); 2.676 (0. 6); 2.672 (0. 8); 2.668 (0.6); 2.525 (21); 2.507 (102.9); 2.503 (131.5); 2.498 (97.6); 2.334 (0.7); 2330 (09); 2. 325 (0.6); 2122 (160) 1.718 (1 .;3) 1713 (1 .;4) 1.484 (1)0); 1002 (08); 0.987 (0.8); 0.000 (1.9) Example l-T3-104: 'H-NMR (400.0 MHz. O): 8: 8.865 (9.2); 8.857 (0.5); 8.845 (6.3); 8.839 (6.4); 8.694 (3.1); 8.683 (3.1); 8.470 (0.5); 8.459 (9.4); 8.229 (6.5); 8.223 (6.4); 7.751 (4.6); 7.728 (0.3); 7.710 (1 'l .3); 4.457 (0.4); 4.403 (0.4); 4.392 (0.4); 4.121 (0.3); 4.108 (1.0); 4.095 (1.0); 4.082 Q4); 3.904 (15.4); 3.395 (0.4): ".70 2015/067647 - 240 — PC'F/EP2014/073795 3.334 (355.8); 3.243 (0.4); 3.175 (4.8); 3.181 (4.8); 2.883 (0.3); 2.873 (0.9); 2.884 (1.2); 2.855 (1.9), 2.845 (1 9), 2. 838 ( .2), 2. 827 (0.9); 2.818(0. 5;) 2.807 (1.7); 2.788 (5.3); 2.789 (5.4); 2.751 (1.8); 2.880 (0.6); 2.878(1.1); 2.871 (1.4) 2.667 (1.1); 2.1542( 0.); 2.525 (4.5); 2.511 (908); 2.507 (1784;) 2.502 (231. 0), 2.498 (188.2), 2.494 (82.9) 2334 (1. 0); 2.329 (1.4;) 2.325 (1. 0); 1.058 (7.2); 1.038 (18.0). 1.019(7.1;) 1002 (18) 0987 (15) 0759 (12) 0748 (35) 0741 (48), 0729 (45) 0723 (37) 0.711 (15) 0588 (15); 0557 (45) 0.551 (43) 0547 (4 0) 0542 (39) 0529(12); 0000 (35) Example 5: 1H-NMR (400.0 MHz. 118-01480): 8: 9.808 (5.9); 8.899 (8.1 ); 8.893 (8.2); 8.882 (8.7); 8.488 (9.0);8.308 (8.0); 8.302 (5.8); 7.753 (4.8); 7.730 (0.3); 7.712 (11.2); 3.904 (12.3); 3.332 (328.2); 3.175 (1.4); 3.181 (1.4); 3.047 (0.5); 0 5;) 2807 (17); 2789 (53) 2770 (54) 2.751 (18.); 2878 (11); 2.871 (1 .;5) 2.667(1 1); 2524 (4.8); 2.511 ; 190.1); 2.502(443) 2.;498(178.1) 2493 (877) 2333 (11); 2329 (15); 2.324(11); 1850 (21) 1838 (53) 1829 (5.8); 1.818(23); 1.295 (2.5); 1. 281 (5 3) 1275 (57) 1260 (21) 1055 (73); 1037 (180) 7.;1) 0000 (32) Example I-T3-106: I1+vale (400.0 MHz. 88-01430): : 8.824 (4.0); 8.818 (4.1); 8.781 (4.7); 8.894 (1.9); 8.883 (1.9); 8.515 (6.0); 8.223 (2.4); 8.198 (4.1); 8.190 (4.0); 7.937 (2.5); 4.458 (0.3); 4.402 (0.4); 4.391 (0.4); 4.107 (0.7); 4.094 (0.8); 3.904 (18.0); 3.332 (223.1); 3.243 (0.4); 3.174 (4.3); 3.181 (4.4); 2.888 (0.5); 2.859 (0.8); 2.850 (1.2); 2.840 (1.2); 2.831 (0.8); 2.822 (0.8); 2.878 (0.9); 2.871 (1 .2); 2.887 (0.9); 2.541 (0.7); 2.525 (3.7); 2.511 (78.4); 2.507 (154.9); 2.502 (201.4); 2.498 (148.3); 2.493 (74.4); 2.334 (0.9); 2.329 (1.2); 2.325 (0.9); 2.147 (13.7); 1.002 (1.8); 0.987 (1.6); 0.755 (0.8); 0.742 (2.2); 0.737 (3.1); 0.725 (2.9); 0.719 (2.4); 0.708 (1.0); 0.583 (1.0); 0.552 (2.9); 0.548 (2.7); 0.542 (2.8); 0.536 (2.5); 0.524 (0.8); 0.000 (2-7) Example 07: ‘H—NMR (400.0 MHz. ds—DMSO): 8: 8.833 (0.5); 8.828 (0.8); 8.819 (2.8); 8.813 (2.8); 8.770 (3.5); 8.503 (0.9); 8.495 (4.3); 8.312 (2.8); 8.308 (2.6); 8.223 (2.0); 8.207 (0.5): 8.201 (0.4); 7.939 (2.1); 3.904 (18.0); 3.332 (177.8); 3.175 (1.5); 3.182 (1.8); 3.027 (12.7); 2.794 (0.5); 2.787 (0.6); 2.778 (1.0); 2.787 (0.8): .780 (2.8); 2.751 (0.4); 2.676 (0.8); 2.872 (1.0); 2.887 (0.7); 2.525 (3.3); 2.511 (87.3); 2.507 (128.5); 2.503 (183.4); 2.498 (118.9); 2.494 (59.0); 2.334 (0.7); 2.329 (1 .0); 2.325 (0.7); 2.158 (9.9); 1.002 (1 .1); 0.987 (1.1); 0.830 (0.3); 0.813 (0.3); 0.808 (0.4); 0.588 (1.8); 0.577 (2.2); 0.568 (0.8); 0.545 (1.0); 0.534 (1.7); 0.518 (1.5); 0.000 (2.1) e l-T3-108: ‘H-NMR (400.0 MHz. 88-01480): 8: 9.804 (5.0); 8.878 (4.1); 8.872 (4.2); 8.793 (5.7); 8.519 (7.0); 8.277 (4.3); 8.271 (4.2); 8.225 (3.2); 7.938 (3.2); 4.458 (0.3); 4.404 (0.4); .393 (0.4); 4.123 (0.4); 4.110 (1.1); 4.097 (1.1); 4.083 (0.4); 3.904 (18.0); 3.433 (0.4); 3.337 (510.1); 3.270 (0.6); 3.258 (0.4); 3.242 (0.4); .175 (4.2); 3.182 (4.3); 3.043 (0.4); 2.872 (0.4); 2.672 (1.4); 2.508 (184.9); 2.503 (232.7); 2.499 (181.4); 2.329 (1.4); 2.148 (15.8); 1.643 (1.8); 1.829 (4.1); 1.822 (4.4); 1.809 (1.8); 1.293 (1.8); 1.280 (4.1); 1.273 (4.3); 1.259 (1.8); 1.002 (1 .2); 0.987 (1.2); 0.000 (0.9) Example 133-109: 1H-NMR (400.0 MHz. O): 8: 8.821 (4.5); 8.815 (4.5); 8.727 (8.7); 8.883 (2.3); 8.872 (2.3); 8.458 (8.9); 8.191 (4.8); 8.185 (4.4); 7. 811 (3.0); 7.577 (3.0); 4.112 (0.4); .099 (0.5); 3.904 (18.0); 3.433103); 3.422 (0.4); 3.341 (478.8); 3.283 (0.5); 3.272 (0.4); 3.289 (0. 4); 3.257 (0.4); 3.243 (0.3); 3.175 (2.2): 3.162 (2.3); 2.888 (0.8); 2.858 (0.9); 2.850 (1.4); 2.840 (1.4); 2.831 (0.9); 2.821 (0.7); 2.878 (0. 9); 2. 872 (1.2); 2.887 (0.9); 2.542 (0.7); 2.525 (3.9); 2.511 (83.9); 2.507 (159.5); 2.503 (202.9); 2.498 (149.8); 2.443 (1.3); 2.424 (3.5); 2.405 (3.5); 2.387 (1.2); 2.334 (0.9); 2.330 (1.2); 2.325 (0.9); 2.098 (18.0); 1.189 (1.4); 1.035 (5.1); 1.018 (10.9); 1.002 (2.2); 0.997 (5.0); 0.987 (1.4); 0.755 (0.9); 0.742 (2.7); 0.737 (3.5); 0.725 (3.4); 0.719 (2.8); 0.708 (1.1); 0.583 (1.1): 0.553 (3.4); 0.547 (3.3); 0.543 (3.1); 0.537 (3.0); 0.525 (0.9); 0.000 (2.0) Example 1110: 1H-NMR (400.0 MHz. ds-DMSO): 8:9.594 (4.8); 8.875 (3.8); 8.889 (3.9); 8.742 (8.3); 8.462(6 .;5) 8272 (3 9) 8.288(3 .;9) 7.813(3 3); 7578 (3.3);4.108 (0.5); 4.095 (0.5); 3904(124); 3.405 (0.3); 3.334 (307.0); 3.289 (0.5); 3.258( .4;) 3242 (04) 3175 (22) 3.161 (2. 3); 3043 (04); 2.871 (0.4); 2.671 (1.3): 2.502 (210.8); 2.445 (1.6); 2.428 (3.8); 2.407 (3.7); 2.388 (14;) 2329 (13); 2097 (180) 1845 (1 5); 1830 (41) 1824 (4.4); 1.610(18): 1.291 (1.8);1.277(4.2);1.271 (4.6);1.256(1.7);1.235(05),169(10),1036(48).1018(10.0), 0.999(5;.;0)0987(12)0.000(24) Example 1111; 1H-NMR (400.0 MHz. d6-DMSO)! 8: 8.917 (0.5); 8.913 (0.5); 8.882 (1.9); 8.878 (1.9); 8.782 (2.8); 8.753 (0.7); 8.503 (3.1); 8.481 (0.8); 8.419 ( .;5) 8.414 (0.5); 8.284 (1.9), 8.279(18); 8.223 (2.2);7938 (2.3); 3.904 (18.0); 3.334 (271.2); 3.175 (0.9); 3.182(10); 3.131 (2.1); 2.919( .;2) 2878 (08); 2872 (10); 2.887 (0.8); 2.525 (3.1); 2.511 (88.1); 2.507 (129.1); 2.503 (188.9);2.498(1219);2.494 (80.4); 2.334 (0.8); 2.329(10); 2325 (08) 2149 (11.9); 1.718 (1.7); 1.712 (1.9); 1.487 (1.3); 0.000 (2.8) Example I-T3112: 1l-I-NMR (400.0 MHz. ds—DMSO): 8: 8843 (55) 8825 (40); 8819(4 0) 8.701 (2.1.) 8.2890(0;) 8. 581 (8.3); 8.513(3.0); 8.198 (3.9); 8.192 (3.8); 8.094 (2.9); 4.109 (0.4); 4096 (05) 3904 (180) 3333 (2184) 3287 (04) 3.2174(5); 3. 162 (26) 2870 (08) 2860 (09) 2.851 (1. 3); 2.841 (1 .;3) 2833 (09) 2.823 (0.8); 2.878 (0.9); 2.871 (1.2); 2.667 (0.9) 2524 (38); 2.7(1499) 2502 (1940); 2498 (1440) 2333 (09); 2329 (12); 232550 (0.9); 1.002(12); 0.987 (1.2); 0.758 (0.8); 0.743 (2.5); 0.387 (3. 3;) 0.728 (31;) 0.720 (2.6); 0.709 (1.0); 0564 (10); 0.553 (32) 0.547 (3.1); 0.544 (2.9); 0.538 (2.8); 0.528 (0.8); 0.000 (2.3) Example I-T3-113: 1H—NMR (400.0 MHz. O): 6: 8.831 (3.5); 8.818 (2.5); 8.812 (2.5); 8.547 (0.8); 8.540 (3.7); 8.512 (1.9); 8.325 (2.4); 8.319 (2.4); 8.213 (0.4); 8.207 (0.4); 8.096 (1.8); 3.904 (16.0); 3.381 (0.4); 3.332 (195.5); 3.175 (1.3); 3.161 (1 .4); 3.028 (11.1); 2.794 (0.5); 2.787 (0.5); 2.777 (0.9); 2.767 (0.7); 2.760 (2.4); 2.676 (0.7); 2.672 (0.9); 2.667 (0.7); 2.525 (2.8); 2.511 (58.6); 2.507 (114.3); 2.502 (147.1); 2.498 (107.3); 2.494 (52.8); 2.334 (0.6); 2.329 (0.9); 2.325 (0.6); 1.002 (1.0): 0.987 (0.9); 0.585 (1.4); 0.577 (1.9); 0.568 (0.7); 0.545 (0.8); 0.534 (1.4); 0.516 (1.3); 0.000 (2.0) Example 14: 1H-NMR (400.0 MHz. de-DMSO): 8: 9.607 (2.4); 8.880 (2.4); 8.874 (2.4); 8.854 (3.1); 8.566 (3.7); 8.515 (1.6); 8.282 (2.4); 8.276 (2.4); 8.095 (1.6); 4.108 (0.4); 4.095 (0.4); 3.904 (16.0); 3.334 (175.5), 3.175 (2.1); 3.161 (2.1); 3044 (0.5); 2.872 (0.5); 2.676 (0.6); 2.672 (O. 8); 2. 667 (0.6); 2.541 (0. 5); 2.525 (2. 4); 2. 511 (50.8); 2. 507 (99.8); 2.502 (129.1); 2.498 (94.9); 2.494 (47.4); 2. 334 (O. 6); 2. 329 (0.7); 2. 325 (0.6); 1.643 (0.8), 1. 629 (2 0); 1. 622 (2 2), 1.608 (0. 9); 1.298 (1. 0); 1.284 (2. 0); 1278 (2.2); 1263 (08); 1002 (09); 0.987 (0.8); 0000 (10.) Example 1-T3-115: 1H—NMR (400.0 MHz. (18—DMSO): 8: 8.898 (1.1); 8.630 (1.1); 8.376 (O. 7); 7.972 (0.4); 7. 595 (4. 0); 3. 903 (4 3), 3. 328 (177. 7); 2876 (1. 2); 2.675 (O. 9); 2. 671 (12); 2.667 (0.9); 2.541 (0. 9); 2. 506 (159 0); 2.502 (205. 8); 2.498 (157. 5); 2.385 (2. 8); 2. 333 (1 .;0) 2. 329 (1. 3); 2. 324 (1. 0); 2.122 (16.0); 1.686 (06); 1.487 (0.8); 0.000 (1.2) Example (331 18: 1H-NMR (400.0 MHz. ds-DMSO): V170 2015/067647 — 241 — 8.: 8.911 (1.0); 8.880 (3.4); 8.874 (3.4); 8.842 (5.1); 8 810 (1.3); 8.548 (5 8); 8.512 (4.5); 8.428 (0 9); 8.292 (3 4): 8.288 (3 4); 8.093 (4 3)’ 3.904 (4.9); 3.827 (229.2); 8.133 (3.9); 2.918 (18.0); 2.875 (1.2); 2.671 (1.8); 2.887 (1.3); 2.541 (1.5); 2.508 (202.4); 2.502 (261.5); 2 488 (200.8); 2.333 (1.1); 2.829 (1 5). 2.325 (1.2); 1.711 (3.8); 1.488 (2.8); -0.001 (1.3) Example 173—1 17: 1H—NMR (400.0 MHz. d8-DMSO): 8: 8.837 (3.9); 8.832 (8.9); 8.898 (5.5); 8.528 (2.3); 8.517 (2.3); 8.440 (6.7); 8.218 (8.3); 7.955 (3.9); 7.949 (3.9); 7.929 (3.4); 3.904 (3.8); 3.328 (223.0); 2.875 (0.7); 2.885 (1.0); 2.857 (1.5); 2.847 (1.5); 2.838 (1.1); 2.828 (0.7): 2.871 (1.5); 2.502 (230.7); 2.329 (1.4); 2.145 (18.0); 0.738 (0.9); 0.720 (3.8); 0.708 (3.4): 0.702 (3.0); 0.891 (1.1); 0.588 (1.2); 0.555 (3.7); 0.549 (3.8); 0.540 (3.2); 0.527 (0.9); 0.000 (1.2) Example 113-1 18: lH—NMR (400.0 MHz. do-DMSO): 8: 8.825 (3.2); 8.820 (3.1); 8.700 (5.9); 8.438 (7.3); 8.213 (3.4); 8.037 (3.0); 8.031 (3.0); 7.930 (3.5); 7.908 (0.5); 3.904 (11.1); 3.380 (239.1); 3.022 (14.7); 2.779 (0.4); 2.784 (0.9); 2.758 (1.3); 2.743 (1.0); 2.737 (1.0); 2.723 (2.0); 2.878 (1.0); 2.871 (1.3); 2.887 (1.0); 2.542 (1.0); 2.524 (4.1); 2.511 (78.7); 2.507 (153.6); 2.502 (199.9); 2.498 (148.4); 2.392 (13.3); 2.364 (1.8); 2.338 (0.9); 2.329 (1.2); 2.825 (0.9); 2.154 (18.0); 0.817 (0.5); 0.802 (0.5); 0.755 (0.8); 0.484 (4.8); 0.488 (2.5); 0.000 (1.4) Example 19: 1H-NMR (400.0 MHz. de-DMSO): 8: 9.408 (4.7); 8.892 (3.9); 8.888 (3.9); 8.718 (5.8); 8.452 (7.3); 8.217 (2.9); 8.041 (3.8); 8.035 (3.8); 7.932 (3.0); 3.904 (9.3); 3.330 (188.1); 3.175 (1.1); 3.182 (1 .1); 2.878 (0.7); 2.671 (1 .0); 2.887 (0.8); 2.541 (0.9); 2.511 (82.5); 2.507 ); 2.502 (185.2); 2.498 (122.9); 2.333 (0.7); 2.329 (1.0); 2.325 (0.7); 2.147 (18.0); 1.812 (1.5): 1.598 (4.0); 1.591 (4.3); 1.578 (1.8); 1.312 (1.8); 1.299 (4.1); 1.292 (4.2): 1.278 (1.5); 0.000 (1.1) Example 1-13—120: 1H-NMR (400.0 MHz. ds-DMSO): : 8.828 (1.6); 8.821 (1.6); 8.821 (4.1); 8.375 (3.7); 8.025 (1.5); 8.020 (1.6); 7.593 (4.8); 3.908 (7.8); 8.331 (235.8); 3.022 (7.8); 2.758 (0.7); 2.743 (0.5); 2.720 (1.0); 2.871 (1.1); 2.541 (0.9): 2.507 (130.2); 2.502 (188.8); 2.498 (127.0); 2.388 (6.8); 2.359 (0.9); 2.329 (1.0): 2.129 (18.0); 0.482 (2.7); 0.485 (1.4); 0.000 (1.0) Example 1—73-121: 1H—NMR (400.0 MHz. 003011): : 8.838 (18.0); 8.480 (18.4); 8.441 (12.5); 7.871 (1.5); 7.554 (14.8); 2.909 (0.5); 2.899 (1.4); 2.890 (2.1); 2.881 (8.1); 2.871 (8.2); 2.882 (2.1); 2.853 (1.6); 2.843 (0.5); 2.489 (0.5); 2.484 (0.6); 2.480 (0.5); 2.287 (0.5); 2.283 (0.4); 2.245 (0.8); 2.228 (0.6); 2.184 (134.4); 2.128 (74.2): 2.108 (1.2); 2.102 (0.8); 2.098 (0.5); 1.978 (0.8); 1.965 (34.9); 1.959 (10.4); 1.953 (53.7); 1.947 (97.8); 1.941 (132.8); 1.935 (92.8); 1.928 (48.8); 1.829 (0.7); 1.781 (0.4); 1.775 (0.8); 1.789 (0.8); 1.783 (0.5); 1.540 (0.4); 1.470 (0.3); 1.429 (0.3); 1.320 (1 .0); 1.289 (9.8): 1.135 (0.4); 0.897 (0.4); 0.881 (1.1); 0.884 (0.5); 0.834 (1.8); 0.821 (4.8); 0.818 (8.9); 0.808 (8.8); 0.798 (5.3); 0.788 (2.4); 0.784 (0.4); 0.748 (0.4); 0.721 (0.4); 0.710 (0.4); 0.681 (2.4); 0.889 (8.3); 0.883 (8.5); 0.859 (5.7); 0.853 (5.3); 0.841 (1.8); 0.000 (1.3) Example 113-122: lH-NMR (400.0 MHz. : 8: 8.795 (7.1); 8.792 (7.1); 8.712 ; 8.398 (7.3); 8.898 (7.2); 8.249 (14.8); 8.280 (0.4); 8.035 (5.4); 8.031 (10.0); 8.027 (5.8); 7.832 (3.8); 7.830 (4.9); 7.828 (3.7); 7.821 (2.0); 7.814 (5.0); 7.810 (5.4); 7.716 (5.3); 7.700 (3.9); 7.897 (5.2); 7.585 (0.4); 7.519 (5.8); 7.500 (9.9); 7.480 (4.3); 7.146 (1.9); 4.088 (0.4); 4.088 (1.8); 4.050 (1.3); 4.033 (0.5); 2.907 (0.8); 2.897 (1.9); 2.888 (2.8); 2.879 (4.2); 2.889 (4.1); 2.881 (2.8); 2.851 (2.0); 2.842 (0.7); 2.488 (0.7); 2.483 (0.9); 2.459 (0.7); 2.266 (0.3); 2.250 (0.4); 2.144 (888.5); 2.120 (3.2); 2.114 (4.0); 2.108 (51); 2.101 (3.3); 2.095 (1.7); 2.018 (0.5); 2.014 (0.5); 1.972 (7.8); 1.984 (22.8); 1.958 (55.1); 1.952 (312.9); 1.948 (568.6): 1.940 (788.2); 1.984 (528.3); 1.928 (270.3); 1.787 (0.4); 1.781 (1.7); 1.775 (3.2); 1.769 (4.4); 1.782 (8.0); 1.758 (1.5); 1.437 (5.8 ) : 1.358 (0.3); 1.338 (0.6); 1.319 (0.4): 1.285 (0.5); 1.270 (2.2); 1.222 (1.8); 1.204 (3.0); 1.188 (1.6); 1.089 (0. ); 0.881 (0.4); 0.793 (2.2) ; 0.781 (8.2); 0.775 (8.7); 0.783 (8.9): 0.757 (6.5); 0.746 (3.2); 0.724 (0.5); 0.707 (0.5); 0.887 (0.5); 0.677 (0 11>": ); 0.847 (3.3); 0.837 (8.3;) 0.630 (8.0); 0.828 (7.0); 0.820 (8.8); 0.808 (2.2); 0.008 (1.7); 0.000 (80.4); 0.009 (2.1) e 3: ‘H-NMR (400.0 MHz. O): 8: 8.894 (2.1); 8.708 (1.4); 8.439 (1.2); 8.213 (2.9); 7.984 (0.8); 7.980 (3.0); 3.904 (15.2); 3.331 (445.1); 3.174 (0.5); 3.181 (0.5); 8.121 (0.5); 2.877 (2.5); 2.675 (1.8); 2.871 (1.8); 2.887 (1.4); 2.542 (1.7); 2.508 (224.4); 2.502 (292.1); 2.498 (219.8); 2.389 (5.1); 2.333 (1.3); 2.329 (1.8); 2.325 (1 .4); 2.148 (18.0); 1.887 (1.2); 1.492 (1.5); 1.418 (0.8); 1.249 (0.4); 1.235 (0.4); 0.000 (1.8) Example l-T3-124: 1H-NMR (400.0 MHz. 118-01480): 8: 8.836 (5.2); 8.831 (5.2); 8.758 (7.5); 8.544 (2.8); 8.534 (2.9); 8.502 (4.3); 8.488 (8.8); 8.087 (4.0); 7.952 (5.0); 7.948 (5.0); 4.487 (0.8); .454 (2.0); 4.440 (0.8); 4.113 (0.5); 4.100 (0.5); 3.904 (18.0); 3.507 (0.4); 3.482 (0.5); 3.488 (0.5); 3.458 (0.5); 3.395 (5.7); 3.388 (4.9); 3.381 (6.3); 3.340 (838.4); 3.174 (2.4); 3.181 (2.3); 2.888 (0.3); 2.878 (0.9); 2.867 (1.2); 2.858 (1.9); 2.848 (1.9); 2.840 (1 .3); 2.880 (0.9); 2.820 (0.4); 2.878 (1.8); 2.872 (2.1); 2.887 (1.7); 2.507 (284.8); 2.503 (344.8); 2.498 (274.4); 2.334 (1.5); 2.329 (2.0); 2.325 (1.5); 1.273 (0.4): 1.258 (0.8); 1.242 (0.8); 0.873 (0.4); 0.739 (1.2); 0.726 (3.4); 0.721 (4.8); 0.709 (4.3); 0.708 (3.7); 0.892 (1 .5); 0.587 (1.5); 0.558 (4.6); 0.550 (4.3); 0.548 (4.1); 0.540 (3.8); 0.528 (1.1 ); 0.008 (2.2); 0.000 (80.2); -0.008 (2.5) Example l-T3-125: 1H-NMR (400.1 MHz. de-DMSO): 8: 9.41 (0.0144); 8.89 8); 8.83 (0.0014); 8.77 (0.0184); 8.49 (0.0301); 8.23 (0.0012); 8.09 (0.0103); 8.03 (0.0119); 3.31 0); .54 9); 2.50 (0.2387); 1.59 (0.0138); 1.30 (0.0138); 0.15 (0.0007); 0.00 (0.1822); -0.16 (0.0004) Example l-T3-126: 1H-NMR (400.0 MHz. do-DMSO): 8: 9.406 (0.9); 8.069 (2.0); 7.667 (0.4); 7.646 (1.1); 7.621 (0.6); 7.616 (0.6); 7.538 (0.8); 7.533 (0.7); 6.479 (0.9); 3.322 (20.1); 2.524 (0.4); 2.519 (0.7); 2.511 (11.8); 2.506 (24.6); 2.502 ; 2.497 (24.8); 2.493 (12.4); 1.989 (0.8); 1.608 (0.4); 1.594 (0.8); 1.587 (0.9); 1.574 (0.4); 1.398 (16.0); 1.291 (0.4); 1.278 (0.7); 1.271 (0.8); 1.257 (0.3); 1.175 (0.5); 0.008 (0.6); 0.000 (18.6); -0.009 (0.7) Example l-T3-127: lH-NMR (400.0 MHz. d8-DMSO): 6: 8.850 (5.1); 8.845 (5.4); 8.692 (9.2); 8.530 (3.1); 8.520 (3.2); 8.464 (9.2); 8.273 (16.0); 7.973 (5.1); 7.967 (5.3); 4.105 (0.5); 4.091 (0.5); 3.903 (5.0); 3.329 ; 3.175 (1.9); 3.162 (1.8); 2.877 (0.8); 2.868 (1.2); 2.859 (1.9); 2.849 (1.9); 2.840 (1.3); 2.831 (0.9); 2.820 (0.3); 2.672 (0.6); 2.667 (0.5); 2.507 (79.2); 2.502 (111.9); 2.463 (0.7); 2.334 (0.5); 2.329 (0.6); 0.740 (1.1); 0.727 (3.5); 0.722 (4.8); 0.710 (4.4); 0.704 (4.0);0693 (1.5); 0.571 (1.5); 0.561 (4.6); 4.7); 0.551 (4.6); 0.545 (4.2); 0.533 (1.1); 0.000 (0.4) Example I-T3-128: 1H-NMR (400.0 MHz. de-DMSO): 8: 8.840 (3.6); 8.835 (3.5); 8.698 (8.9); 8.465 (8.7); 8.272 (15.4); 8.058 (3.3); 8.053 (3.4); 7.922 (0.5); 3.903 (5.1); 3.328 (66.8); 3.175 (1.0); 3.162 (1.0); 3.026 (16.0); 2.891 (0.3); 2.784 (0.4); 2.767 (0.9); 2.756 (1.4); 2.746 (1.0); 2.721 (1.9); 2.676 (0.5); 2.672 (0.6); 2.667 (0.5): 2.542 (0.7); 2.511 (37.1); 2.507 (71.3); 2.503 (93.3); 2.498 (71.7); 2.395 (14.5); 2.369 (1.9); 2.334 (0.4); 2.329 (0.6); 2.325 (0.4); 0.819 (0.5); 0.803 (0.5); 0.758 (0.6); 0.481 (5.4); 0.463 (2.8); 0.000 (0.4) V170 2015/067647 PCT/EP27014/073795 [Example 2911H-NMR (400.0 MHz. ISO): 8: 9.412 (6.2); 8.906 (4.7); 8.900 (5 0): 8.710 (9.0); 8.478 (8.5); 8.276 (16.0). 8.063 (4.7), 8.058 (4.9); 3.903 (5.3); 3.434 (0.4); 3.334 (71.6); 3.169 (3 4'). 2.672 (0.8); 2.520 (27.6); 2.507 (94.6); 2.503 (122.2). 2.499 (100.6); 2.329 (0.7); 1.612 (1.9); 1.598 (5.2), 1.591 (5.7); 1.578 (2.3); 1.317 (2.3); 1.304 (5.3); 1.297 (5.6); 1.283 (1.9); 0.000 (0.4) Example l-T3—130: 1H-NMR (400.0 MHz. ds-DMSO): 8: 8.821 (3.6); 8.815 (3.5); 8.760 (6.9); 8.499 (4.1); 8.484 (8.5); 8.085 (3.9); 8.046 (3.3); 8.040 (3.3); 7.911 (0.5); 3.904 (10.2); 3.327 (87.7); 3.176 (0.7); 3.163 (0.7); 3.025 (16.0); 2.779 (0.4); 2.768 (0.8); 2.762 (0.9); 2.753 (1.5); 2.742 (1.1); 2.736 (1.1); 2.724 (2.2); 2.676 (0.5); 2.672 (0.7); 2.667 (0.5); 2.525 (2.4); 2.512 ; 2.507 (81.2); 2.503 (106.8): 2.498 (80.2); 2.494 (41.1); 2.398 (14.3); 2.369 (1.8); 2.334 (0.5); 2.330 (0.7); 2.325 (0.5); 0.820 (0.5); 0.803 (0.5); 0.757 (0.6); 0.485 (4.9): 0.467 (2.7); 0.000 (0.5) Example 1-T3-131: 1H-NMR (400.0 MHz. ds-DMSO): 8: 8.891 (3.3); 8.768 (2.3); 8.499 (5.4); 8.485 (2.0); 8.085 (4.9); 7.990 (1.3); 3.903 ; 3.327 (119.4); 3.175 (0.8); 3.162 (0.9); 3.122 (0.7): 2.879 (3.8); 2.676 (0.7); 2.672 (1.0); 2.667 (0.8); 2.542 (0.7); 2.525 (3.3); 2.511 (61.8); 2.507 (121.8); 2.503 (160.9); 2.498 (122.6); 2.494 (64.2); 2.396 (8.3); 2.334 (0.8); 2.329 (1.0); 2.325 (0.8); 1.686 (1.8): 1.497 (2.2); 1.420 (0.8); 0.000 (0.7) Example 1—13-132; 1H-NMR (400.1 MHz. ds-DMSO): : 8.907 (3.3); 8.899 (3.2); 8.481 (1.9); 8.289 (18.0); 8.002 (1.1); 4.088 (0.5); 4.075 (0.5); 3.311 (245.5); 3.269 (0.3); 3.175 (2.1); 3.182 (2.1); 3.123 (0.6); 2.875 (3.1); 2.710 (0.5); 2.874 (0.4); 2.870 (0.5); 2.540 (120.2); 2.505 (48.9); 2.501 (84.0); 2.497 (45.8); 2.484 (0.3); 2.398 (8.8); 2.387 (0.8); 2.328 (0.5); 2.323 (0.4); 1.888 (1.8); 1.495 (2.0); 1.431 (0.8); 1.423 (0.8); 0.148 (0.4); 0.008 (3.2); 0.000 ; . 0.008 (4.5); 0.150 (0.4) Example 103—133; 1H-NMR (400.1 MHz. 56-01480): 8: 8.822 (3.7); 8.817 (3.4); 8.750 (9.7); 8.470 (9.1); 8.094 (15.1); 8.040 (3.3); 8.035 (3.3); 7.903 (0.4); 3.311 (88.3); 3.287 (0.3); 3.028 (16.0); 2.781 (0.4); 2.785 (1.0); 2.754 (1.5); 2.743 ( .1); 2.738 (1.1); 2.721 (1.8); 2.711 (0.7); 2.555 (0.4); 2.554 (0.5); 2.553 (0.8); 2.552 (0.7); 2.550 (0.8); 2.549 (1.0); 2.540 (89.5); 2.529 (0.7); 2.528 (0.8); 2.527 (0.8); 2.525 (0.8); 2.524 (0.8); 2.523 (0.6); 2.522 (0.6); 2.510 (12.1); 2.505 ; 2.501 (31.3); 2.497 (21.3); 2.492 (9.9); 2.395 (14.5); 2.371 (1.7); 0.819 (0.4); 0.804 (0.5); 0.755 (0.8); 0.482 (5.8); 0.484 (3.0); 0.013 (0.3); 0.011 (0.4); 0.008 (2.1); 0.007 (1.4); 0.000 (81.4); -0.006 (1.7); 0.009 (2.2); 0.013 (0.4); 0.014 (0.3) Example I-T3-134: 1H-NMR (400.0 MHz. da-DMSO): 8: 8.823 (4.4); 8.427 (4.3); 8.403 (0.4); 8.263 (1.3); 8.242 (1.6); 8.112 (2.9); 8.071 (2.1); 8.050 (1.8); 7.818 (2.7); 7.813 (2.7); 7.760 (1.6): .755 (1.5); 7.747 (1.0); 7.739 (1.8); 7.734 (1.5); 7.724 (0.9); 7.560 (1.0); 7.553 (2.6); 7.540 (1.0); 7.532 (2.1); 3.327 (28.9); 3.321 (6.8); 3.015 (11.5); 2.766 (0.4); 2.756 (0.8); 2.748 (1.0); 2.740 (1.3); 2.730 (1.2); 2.716 (2.7); 2.676 (0.4); 2.673 (0.4); 2.507 ; 2.503 (53.0); 2.499 (41.0); 2.330 (0.4); 2.076 ; 2.068 (2.0); 1.170 (0.4); 0.820 (0.4); 0.812 (0.4); 0.804 (0.4); 0.757 (0.5); 0.748 (0.5); 0.559 (2.6): 0.551 (2.5); 0.503 (0.4); 0.472 (2.1); 0.455 (2.2); 0.000 (51.7); -0.009 (7.9) Example 1135: 1H-NMR (400.1 MHz. 56-01450): : 8.547 (0.5); 8.505 ; 8.454 (9.8); 8.448 (8.1); 8.442 (4.1); 8.281 (10.0); 8.068 (16.0); 7.686 (8.9); 7.880 (8.8); 3.588 (0.4); 3.410 (4.1); 3.394 (11.2); 3.378 (4.3); 3.309 (185.8); 3.288 (0.7); 2.832 (0.3); 2.822 (0.9); 2.812 (1 .3); 2.804 (2.0); 2.794 (2.0); 2.785 (1 .3); 2.778 (0.9); 2.765 (0.4); 2.710 (0.9); 2.874 (0.5); 2.889 (0.6); 2.885 (0.5); 2.580 (0.6); 2.540 (228.8); 2.523 (1.6); 2.509 (31.4); 2.505 (60.7); 2.500 (78.7); 2.496 (53.0); 2.492 (24.2); 2.388 (0.8); 2.332 (0.4); 2.327 (0. ); 2.323 (0.4); 1.887 (4.2); 1.871 (11.1); 1.854 (3.9); 1.235 (0.4); 0.704 (1.4); 0.891 (3.7); 0.888 (5.2); 0.874 (4.8); 0.888 (4.0); 0.857 (1.7); 0.547 (1.8); 0.538 (5.3); 0.530 (4.6); 0.528 (4.3); 0.520 (4.2); 0.508 (1.3); 0.146 (0.5); 0.008 (4.2); 0.000 (120.8); -0.008 (4.5): 0.150 (0.5) Example I-T3-136: 1H-NMR (400.0 MHz. da-DMSO): : 8.510 (2.8); 8.502 (7.1); 8.497 (8.4); 8.441 (8.5); 8.259 (8.4); 8.129 (2.2); 8.117 (2.5); 8.108 (1.0); 8.088 (5.7); 8.080 (18.0); 4.487 (1.4); 4.453 (4.0); 4.439 (1.5); 4.111 (0.4); 4.099 (0.4); 3.904 (15.8); 3.804 (0.4); 3.483 (0.4); 3.470 (0.5); 3.455 (0.4); 3.395 (8.9); 3.388 (7.6): 3.381 (9.5); 3.338 (810.3); 3.174 (1.7); 3.181 (1.8); 2.953 (0.4); 2.932 (11.5); 2.920 (11.5); 2.847 (0.4); 2.837 (0.9); 2.828 (1 .3); 2.819 (1.9); 2.810 (1.9); 2.801 (1.3); 2.792 (0.9); 2.783 (0.4); 2.871 (2.2); 2.818 (0.3); 2.508 (280.8); 2.502 (354.5); 2.498 (275.8); 2.329 (2.2); 1.234 (0.8); 0.873 (0.6); 0.854 (0.5); 0.742 (1.0); 0.724 (4.4); 0.711 (4.1); 0.708 (3.8); 0.894 (1.4); 0.587 (1.5); 0.578 (4.6); 0.570 (4.4); 0.581 (3.8); 0.548 (1 .1); 0.000 (48.0) Example 1-13—137; 1H—NMR (400.0 MHz. d6-DMSO)I 8: 8.543 (8.9); 8.537 (7.0); 8.455 (8.0); 8.384 (2.9); 8.358 (3.0); 8.288 (8.1); 8.118 (4.5); 8.113 (4.5); 8.083 (13.0); 4.487 (0.5); 4.453 (1.5); 4.439 (0.6); 4.112 (0.4); 4.099 (0.4); 3.904 (18.0); 3.483 (0.3); 3.489 (0.4); 3.433 (0.5); 3.407 (0.8); 3.395 (4.1); 3.388 (3.4); 3.381 (4.6); 3.338 (731.2); 3.174 (1.7); 3.151 (1.6); 2.955 (0.8); 2.852 (0.8); 2.844 (1.2); 2.835 (1.8); 2.828 (2.0); 2.818 (2.0); 2.809 (2.0); 2.800 (2.0); 2.791 (1.8); 2.782 (1.2); 2.772 (0.8); 2.878 (1.4); 2.672 (1.9); 2.887 (1.5); 2.507 ); 2.502 (302.0); 2.498 (229.8); 2.333 (1.4); 2.329 (1.8); 2.325 (1.4); 1.237 (0.4); 0.873 (0.4); 0.854 (0.3); 0.785 (1.1); 0.753 (3.5); 0.748 (4.4); 0.738 (5.1); 0.731 (4.0); 0.718 (5.1); 0.706 (3.9); 0.700 (3.5); 0.889 (1.4); 0.582 (1.4); 0.571 (4.3); 0.585 (4.0); 0.558 (3.5); 0.544 (1.0); 0.466 (1.3); 0.455 (4.0); 0.450 (4.1); 0.445 (4.0); 0.440 (3.9); 0.428 (1 .1); 0.000 (395) Example I-T3-138: ‘H-NMR (400.0 MHz. d8-DMSO): 8: 8.524 (1.8); 8.515 (1 9); 8.487 (3.8); 8.482 (3.9); 8.443 (8.4); 8.432 (1.1); 8.419 (1.9); 8.405 (1.0); 8.274 (0.4); 8.262 (8.3); 8.120 (4.0): 8.114 (3.8); 8.081 (10.3); 4.453 (0.7); 3.904 (18.0); 3.808 (1.0); 3.592 (3.0); 3.579 (3.7); 3.588 (1.8); 3.523 (3.7); 3.511 (4.9); 3.498 (1.9); 3.473 (0.5); 3.449 (0.3); 3.395 (2.5); 3.387 (2.3); 3.381 (2.9); 3.338 (558.7); 3.299 (28.1); 3.288 (1.6); 3.282 (0.8); 3.258 (0.7); 3.174 (0.9); 3.181 (0.9); 2.840 (0.8); 2.831 (0.9); 2.822 (1.3); 2.812 (1.4); 2.804 (0.9); 2.795 (0.8); 2.676 (1.4); 2.872 (2.0); 2.667 (1.4); 2.507 (219.1); 2.503 (282.2); 2.498 (210.9); 2.334 (1 .2); 2.329 (1.7); 2.325 (1 .3); 1.235 (0.5); 0.747 (0.8); 0.734 (2.3); 0.729 (3.2); 0.717 (2.9); 0.711 (2.8): 0.700 (1.0); 0.589 (1 .1); 0.579 (3.3); 0.573 (3.0); 0.569 (3.0); 0.583 (2.7); 0.551 (0.9); 0.008 (1.7); 0.000 (45.2); —0.008 (1.8) Example 103-139: 1H—NMR (400.0 MHz. 05.011430): 8: 9.474 (2.4); 8.837 (1.9); 8.831 (2.1); 8.802 (3.2); 8.355 (3.4); 7.970 (2.0); 7.985 (2.2); 7.598 (4.3); 4.467 (0.4); 4.453 (1.0); 4.440 (0.4); 3.904 (8.3); 3.423 (0.3); 3.395 (2.3); 3.387 (2.3); 3.381 (2.8); 3.340 (340.7); 3.174 (0.4); 3.161 (0.4); 3.083 (0.8); 2.880 (0.8); 2.872 (0.9); 2.668 (0.7); 2.507 (107.5); 2.503 (142.8); 2.498 ); 2.329 (1.2); 2.325 (1.2); 2.312 (0.8); 2.299 (0.6); 2.292 (0.5); 2.110 (18.0); 1.815 A0.8); 1.601 (2.0); 1.594 (2.3); 1.581 (1.0); 1.324 (0.9); 1.310 (2.1); 1.304 (2.3); 1.289 (0.8); 1.257 (0.4); 1.243 (0.4); 1.168 (0.4); 0.993 (2.1); 0.982 (3.3); 0.962 (1.9); 0.000 (10.4) Example 1-T3-140: 1H-NMR (400.0 MHz. (11.01480) 8: 8.785 (2.0); 8.780(19); 8.595 (1.3); 8.584 (4.5); 8.345 (3.4); 7.890 (20); 77.885419); 7594.142924455 (0.3); 3.904 (3.2); 3.408(05); V170 2015/067647 - 243 — 3.394 (1 3); 3.382 (1.7); 3 342 (322.7); 3.174 (0.4); 3.152 (0 4); 2.892 (0.5); 2.883 (0 7). 2.873 (0.7). 2.865 (0 5); 2.855 (0.4); 2.572 (0.7) 2.503 (1 10.1). 2.352 (0.4); 2.345 (0.5); 2.334 (1.3); 2.314 (0.5); 2.111 (16.0); 0.973 (1.9); 0.951 (1 8). 0.951 (1.9); 0.931 (1.5); 0.740 (0.4). 0,723 (1 7); 0 710 (1 7); 0.705 (1.4) 0.894 (0.8); 0.582 (0 5); 0.571 (1.8); 0 554 (1 8); 0.555 (1.5). 0.543 (0 4); 0 000 (8.3) Example 1—13-141: 1H~NMR (400.0 MHz. 58—01480); : 9.093 (2.2); 8.558 (2.1); 8.552 (2.2); 8.577 (3.2); 8.327 (3.3); 8.314 (2.3); 8.308 (2.2); 7.593 (3.8); 3.989 (10.4); 3.904 (3.5); 3.409 (0.5): 3.343 (332.3); 3.285 (0.3); 2.676 (0.5); 2.872 (0.7); 2.588 (0.6); 2.525 (2.4); 2.512 (45.5); 2.507 (89.1); 2.503 (118.0); 2.498 (87.1); 2.334 (0.5); 2.330 (0.7); 2.325 (0.5); 2.121 (18.0): 1.502 (0.8); 1.587 (2.0); 1.581 (2.2); 1.557 (0.9); 1.305 (1.0); 1.292 (2.1); 1.285 (2.2); 1.271 (0.8); 0.008 (0.4); 0.000 (11.5); -0.008 (0.5) Example l—T3—142: 1H-NMR (400.0 MHz. 08-01180); 8: 8.787 (2.0); 8.582 (3.2); 8.343 (3.2); 7.948 (2.0); 7.851 (0.3); 7.591 (5.1); 4.454 (0.8); 3.904 (4.5); 3.381 (3.9); 3.341 (345.8); 3.218 (0.4); 3.175 (0.5); 3.152 (0.4); 3.043 (7.9); 2.791 (1.0); 2.781 (0.9); 2.755 (1.5); 2.572 (1.0); 2.503 (159.1); 2.830 (1.0); 2.122 (15.0); 1.928 (0.8); 1.915 (0.9); 1.901 (0.7); 1.882 (0.4); 0.992 (1.5); 0.981 (2.3); 0.943 (2.0); 0.824 (0.4); 0.809 (0.4); 0.754 (0.5); 0.540 (2.1); 0.482 (1.7); 0.457 (1.8); 0.000 (14.1) Example 113-143: ‘H-NMR (400.0 MHz. 113-01430): 8: 8.508 (2.1); 8.802 (2.1); 8.555 (3.2); 8.308 (3.3); 8.288 (1.0); 8.255 (1.0); 8.227 (2.2); 8.221 (2.1); 7.590 (3.9); 3.948 ; 3.904 (3.5); 3.395 (0.9); 3.343 (295.5); 3.175 (0.3); 2.873 (0.3); 2.853 (0.5); 2.855 (0.7); 2.845 (0.7); 2.537 (0.5); 2.827 (0.3); 2.575 (0.5); 2.572 (0.7); 2.558 (0.5); 2.507 (88.5); 2.503 (112.5); 2.498 (84.8); 2.334 (0.5); 2.329 (0.7); 2.325 (0.5); 2.120 (18.0); 0.740 (0.4); 0.727 (1.3); 0.72 (1.8); 0.709 (1.6); 0.704 (1.4); 0.592 (0.8); 0.580 (0.8); 0.570 (1.8); 0.554 (1.7); 0.554 (1.4); 0.542 (0.4); 0.008 (0.7); 0.000 (14.5) e 1—13-144: 1H-NMR (400.0 11451258011180); : 8.553 (2.0); 8.558 (2.0); 8.525 (3.5); 8.302 (3.3); 8.005 (1.9); 7.999 (2.0); 7.590 (4.5); 4.458 (0.3); 4.454 (0.8); 4.440 (0.3); 3.915 (9.8); 3.904 (7.4); 3.425 (0.4); 3.395 (2.5); 3.388 (2.3); 3.381 (3.0); 3.341 (345.9); 3.282 (0.4); 2.981 (8.7); 2.748 ( .5); 2.738 (0.8); 2.724 (0.8); 2.711 (0.3); 2.700 (0.9); 2.875 (0.7); 2.872 (0.9); 2.858 (0.8); 2.507 (111.1); 2.503 (144.8); 2.499 (113.9); 2.334 (0.8); 2.329 (0.8); 2.127 (15.0); 0.488 (3.1); 0.449 (1.7); 0.000 (11.5) Example 113-145; 1l-l—NMR (400.0 MHz. 53—01480): 8: 8.848 (0.8); 8.841 (0.8); 8.835 (4.1); 8.829 (4.2); 8.781 (5.9); 8.537 (7.1); 8.315 (0.4); 8.283 (13.4); 8.274 (4.8); 8.257 (0.5); 8.251 (0.5); 3.424 (0.3); 3.409 (0.3); 3.398 (0.4); 3.387 (0.3); 3.371 (0.4); 3.324 (185.3); 2.775 (0.4); 2.784 (0.8); 2.759 (0.9); 2.750 (1.8); 2.739 (1.0); 2.733 (0.9); 2.722 (0.5); 2.875 (1.1); 2.871 (1.5); 2.587 (1.1); 2.524 (4.5); 2.505 (173.0); 2.502 (225.3); 2.497 (157.2); 2.333 (1.1); 2.329 (1.5); 2.324 (1.1); 1.398 (15.0); 1.238 (4.1); 1.220 (8.5); 1.202 (3.9); 1.120 (0.5); 1.102 (1.0); 1.085 (0.5); 0.951 (0.4); 0.935 (0.5); 0.577 (2.8); 0.549 (2.5); 0.532 (2.1); 0.145 (0.9); 0.008 (7.2); 0.000 (188.0); 0.008 (8.4); 0.150 (0.9) Example 113-145; ‘H—NMR (400.0 MHz. 83.011130): 8: 10.752 (3.5); 8.900 (3.8); 8.894 (3.7); 8.808 (5.3); 8.571 (5.2); 8.570 (5.2); 8.393 (3.7); 8.387 (3.8); 8.284 (8.3); 8.283 (8.3); 8.028 (4.8); 7.502 (4.8); 7.501 (5.0); 5.758 (5.9); 4.058 (0.5); 4.038 (1.5); 4.020 (1.5); 4.002 (0.5); 3.837 (18.0); 3.324 (33.1); 2.871 (0.4); 2.524 (1.0); 2.520 (1.4); 2.511 (20.1); 2.507 (41.3); 2.502 (54.9); 2.497 (40.1); 2.493 (19.7); 2.329 (0.4); 1.989 (5.9); 1.193 (1.9); 1.175 (3.8); 1.157 (1.9); 0.008 (1.9); 0.000 (58.8); 0.009 (2.2) Example 1—13-147; 1H-NMR (400.0 MHz. de-DMSO): : 8.999 (3.5); 8.993 (3.5); 8.778 (8.5); 8.499 (5.5); 8.384 (3.5); 8.378 (3.5); 8.279 (10.7); 5.757 (1.1); 4.384 (1 .5); 4.385 (5.0); 4.348 (5.1); 4.381 (1.7); 3.894 (0.5); 3.324 (128.8); 2.714 (15.0); 2.875 (0.9); 2.871 (1.3); 2.555 (1.0); 2.524 (3.3); 2.511 (89.0); 2.508 (138.7): 2.502 (184.5); 2.498 (139.2); 2.333 (0.8); 2.329 (1.1); 2.325 (0.9); 1.989 (0.7); 1.377 (5.4); 1.350 (11.3); 1.342 (5.4); 1.234 (0.5); 1.175 (0.4); 0.145 (0.9); 0.008 (8.9); 0.000 (189.8); -0150 (0.9) Example I-T3-148: 1H-NMR (400.0 MHz. : 6: 8.344 (1.0); 8.180 (2.1); 8.179 (2.0); 8.138 (1.8); 8.094 (1.0); 7.688 (1.2); 7.683 (1.6); 7.655 (0.9); 7.650 (0.6); 7.634 (1.0); 7.629 (0.8); 7.474 (1.5); 7.454 (1.2); 6.895 (0.4); 6.892 (0.4); 2.860 (0.4); 2.851 (0.6); 2.842 (0.6); 2.833 (0.4); 2.132 (17.4); 2.107 (0.3); 1.964 (1.5); 1.958 (3.8); 1.952 (20.1); 1.946 (36.2); 1.940 (48.4); 1.933 (33.3); 1.927 (17.3); 1.437 (16.0); 0.781 (1.0); 0.776 (1.2); 0.763 (1.3); 0.758 (0.9); 0.746 (0.4); 0.611 (0.4); 0.601 (1.1); 0.594 (1.2); 0.590 (1 .0); 0.584 (1.0); 0.000 (2.5) Example 1—13—149: 1H-NMR (400.0 MHz. ds-DMSO): : 18.228 (0.3); 18.070 (0.4); 11.873 (0.3); 9.484 (0.4); 9.435 ; 9.407 (0.4); 9.255 (9.2); 9.158 (18.0); 8.889 (9.9); 8.544 ; 8.514 (0.4); 8.315 (1.1); 8.148 (0.4); 8.012 (0.4); 7.945 (12.0); 7.931 (5.4); 7.910 (5.2); 7.905 (5.4); 7.850 (0.4); 7.843 (0.4); 7.839 (0.4); 7.702 (0.4); 7.539 (0.4); 7.582 (9.8); 7.551 (9.0); 7.543 (0.4); 3.837 (0.4); 3.591 (0.4); 3.572 (0.4); 3.547 (0.4); 3.535 (0.6); 3.512 (0.5); 3.489 (0.6); 3.434 (0.9); 3.392 (2.8); 3.344 (1318.4); 3.339 ); 3.331 (992.7); 3.218 (1.0); 3.211 (0.9); 3.178 (0.5); 3.121 (0.3); 3.058 (0.3); 2.731 (0.4); 2.871 (5.7); 2.838 (0.4); 2.584 (0.4); 2.505 (889.3); 2.502 (847.8); 2.417 (1.1); 2.381 (0.8); 2.333 (4.7); 2.328 (5.7); 2.288 (0.4); 2.283 (0.4); 1.558 (0.3); 1.520 (4.0); 1.505 (11.5); 1.599 (12.3); 1.585 (5.4); 1.546 (0.5); 1.489 (0.4); 1.370 (0.3); 1.350 (0.7); 1.310 (5.0); 1.298 ; 1.290 (12.3); 1.275 (4.4); 1.237 (0.5); 0.145 (2.0); 0.000 (404.8); -0150 (2.2); 3.145 (0.3) Example 50: ’H—NMR (400.0 MHz. 53-01480): : 9.255 (5.5); 9.179 (0.4); 9.144 (12.1); 9.088 (0.8); 8.858 (5.9); 8.853 (8.0); 8.554 (0.5); 8.535 (18.0); 8.525 (4.5); 8.504 (0.7); 8.318 (0.8); 8.292 (0.4); 7.872 (14.1); 7.888 (7.0); 7.855 (5.0); 7.850 (3.3); 7.559 (0.3); 7.534 (7.4); 7.527 (1 .7); 7.518 (1.6); 7.511 (8.7); 3.558 (0.5); 3.488 (0.4); 3.455 (0.4); 3.444 (0.5); 3.341 (578.1); 3.339 (590.5); 3.331 (552.2); 2.875 (0.5); 2.884 (1.2); 2.855 (1.8); 2.848 (2.5); 2.835 (2.5); 2.828 (1 .7); 2.818 (1.3); 2.807 (0.5); 2.878 (2.5); 2.572 (3.7); 2.887 (2.8); 2.552 (1.4); 2.580 (0.4); 2.525 (9.0); 2.520 (13.1); 2.511 ); 2.507 (411.4); 2.502 ); 2.498 (423.2); 2.493 (212.5); 2.458 (0.5); 2.334 (2.7); 2.329 (3.7); 2.325 (2.7); 0.735 (1.7); 0.724 (4.5); 0.718 (8.8); 0.705 (5.1); 0.700 (5.1); 0.889 (2.3); 0.850 (0.3); 0.808 (0.4); 0.578 (2.2); 0.588 (5.4); 0.582 (5.7); 0.558 (5.5); 0.552 (5.2); 0.540 (1 .7); 0.148 (1.7); 0.030 (0.4); 0.024 (0.4); 0.017 (0.5); 0.008 (12.8); 0.000 (401 4); 0.009 (15.0); -0.150 (1.7) Example 51: ‘l-l-NMR (400.0 MHz. de—DMSO). 8: 9.444 (12.0): 9.048 (16.0); 8.890 (7.0); 8.886 (7.3); 8.610 (8.1); 8.605 (7.8); 8.506 (15.9); 8.495 (0.3); 8.317 (4.4); 7.899 (6.5); 7.894 ; 7.885 (2.6); 7.870 (6.7); 7.865 (4.8); 7.579 (9.1); 7.559 (8.2); 3.410 (0.4); 3.383 (0.7); 3.364 (1.2); 3.327 (1576.2); 3.293 (1.2); 2.694 (0.5); 2.676 (8.0); 2.671 (11.2); 2.667 (8.3); 2.643 (0.4); 2.630 (0.4); 2.623 (0.5); 2.599 (0.7); 2.524 (28.8); 2.520 (43.4); 2.511 (594.8); 2.507 9); 2.502 (1623.1); 2.498 (1195.4); 2.493 (589.7); 2.419 (0.6); 2.338 (3.7); 2.333 (7.9); 2.329 ; 2.324 (8.1); 2.320 (4.0); 1.620 (3.9); 1.606 (9.5); 1.599 (10.3); 1.586 (4.4); 1.546 (0.4); 1.342 (0.4); 1.303 (4.6); 1.289 (9.5); 1.282 (10.2); 1.268 (3.8); 1.234 (0.6); 1.148 (0.9); 0.146 (8.7);0049 (0.4); 0.039 (0.7); 0.008 (63.6); 0.0007(18938); -0.009 (67.7); 0.035 (1.3); -0.045 (0.8); 0088 (0.3); 0.150 ‘ — 244 » (8 7) Example 103—152; 1H-NMR (400.0 MHz d8-DMSO)‘ 19.048 (0.6); 9.022 (18.0); 8.893 (8.5). 8.808 (9.0); 8.804 (8.5); 8.543 (8.0); 8.532 (6.0); 8.515 (0.9); 8.498 (15.9); 8.453 (0.3); 8.317 (2.0); 7.901 (0.4). 7.896 (0.4); 7.828 (8.8); 7.823 (11.4); 7.818 (11.0); 7.812 (8.2); 7.882 (0.3); 7.532 (8.5); 7.521 (2.4); 7.510 (7.5); 3.508 (0.4); 3.327 (1034.9); 3.230 (0.5); 3.210 (0.4); 2.874 (0.7); 2.884 (1.8); 2.854 (2.4); 2.848 (3.5); 2.838 (3.5); 2.827 (2.5); 2.817 (1.7); 2.807 (0.8); 2.871 (8.3); 2.822 (0.7); 2.808 (0.8); 2.508 (980.0); 2.502 (1179.0); 2.329 (8.1); 2.297 (0.4); 2.281 (0.3); 1.238 (0.7); 1.149 (0.8); 0.735 (2.2); 0.717 (8.7); 0.705 (8.5); 0.899 (7.0); 0.888 (2.9); 0.888 (0.5); 0.648 (0.4); 0.815 (0.3); 0.803 (0.4); 0.574 (3.0); 0.583 (9.1); 0.556 (9.0); 0.548 (7.5); 0.535 (2.1); 0.525 (0.5); 0.488 (0.3); 0.148 (5.2); 0.000 (1050.7); 0.150 (5.5) Example 53: ‘H-NMR (400.0 MHz. 88-01480); 8: 9.441 (7.1); 9.380 (9.1); 8.980 (4.8); 8.954 (5.0); 8.841 (9.2); 8.581 (3.9); 8.577 (3.9); 8.317 (0.9); 8.188 (1.1); 8.002 (5.1); 7.997 (8.5); 7.989 (3.3); 7.983 (2.5); 7.948 (3.5); 7.942 (3.0); 7.589 (8.2); 7.588 (5.7); 3.430 (0.8); 3.411 (1.9); 3.393 (2.3); 3.378 (2.8); 3.359 (2.8); 3.328 (240.7); 2.950 (0.6); 2.932 (2.1); 2.913 (2.4); 2.898 (2.1); 2.880 (1.9); 2.882 (0.5); 2.878 (1.9); 2.871 (2.7); 2.887 (2.0); 2.542 (1.0); 2.525 (8.8); 2.520 (10.2); 2.511 (145.4); 2.507 (298.8); 2.502 (398.9); 2.498 (292.8); 2.493 ); 2.334 (1.9); 2.329 (2.8); 2.325 (1.9); 2.320 (1.0); 2.075 (0.6); 1.908 (0.5); 1.827 (2.3); 1.813 (5.8); 1.808 (8.0); 1.593 (2.7); 1.314 (2.8); 1.301 (5.8); 1.294 (5.9); 1.279 (2.3); 1.108 (7.4); 1.088 ; 1.089 (7.2); 0.146 (2.3); 0.008 (17.1); 0.000 (509.3); 0.009 ; 0.031 (0.4); 0.034 0.4); 0.150 (2.3) Example I-T3—154: ‘H—NMR (400.0 MHz. ds-DMSO) 8: 9.448 (8.4); 9.231 (4.3); 9.228 (4.3); 9.188 (8.2); 8.834 (4.2); 8.829 (4.2); 8.598 (8.2); 8.317 (3.8); 7.954 (4.3); 7.949 (8.0); 7.934 (3.1), 7.929 (2.0); 7.913 (3.2); 7.908 (2.5); 7.595 (5.2); 7.574 (4.7); 4.152 (1.7); 4.133 (5.6); 4.115 (5.6); 4.098 (1.8); 3.459 (0.4); 3.445 (0.3). 3.438 (0.3); 3.328 (1348.5); 2.894 (0.4); 2.676 (8.7); 2.871 (9.0); 2.887 (8.9); 2.829 (0.5); 2.820 (0.5); 2.524 (24.4); 2.508 (1009.7); 2.502 (1305.6); 2.498 (988.2); 2.405 (0.8); 2.389 (0.8); 2.333 (8.4); 2.329 (8.7); 2.325 (8.5); 1.823 (2.1); 1.808 (5.2); 1.602 (5.6); 1.589 (2.4); 1.575 (0.5); 1.328 (6.4); 1.308 ; 1.289 (11.7); 1.274 (2.1); 1.258 (0.8); 1.247 (0.5); 1.238 (0.7); 1.158 (0.5); 1.147 (0.4); 1.088 (0.8); 0.148 (8.9); 0.008 (82.7); 0.000 (1428.7); 0.059 (0.5); -0.080 (0.4); 0.101 (0.4); 0.150 (7.0) Example 1-13—155; ‘H-NMR (400.0 MHz. 003011): 8: 8.345 (0.9); 8.192 (1.8); 8.153 (1.5); 8.094 (0.9); 7.738 (1.0); 7.732 (1.3); 7.708 (0.8); 7.700 (0.5); 7.885 (0.7); 7.880 (0.8); 7.583 (0.4); 7.507 (1.1); 7.488 (0.9); 2.144 (8.2); 2.114 (0.5); 2.108 (0.4); 1.972 (1.1); 1.984 (1.1); 1.958 (2.8); 1.952 (14.4); 1.948 (28.2); 1.940 ; 1.934 (25.1); 1.928 (13.8); 1.598 (0.5); 1.582 (1.3); 1.575 (1.3); 1.581 (0.7); 1.437 (16.0); 1.382 (0.8); 1.349 (1.3); 1.342 (1.4); 1.327 (0.5); 1.204 (0.5); 0.146 (0.8); 0.008 (7.0); 0.000 (147.1); -0.008 ; 0.150 (0.7) Example 1-13—1 56: 1H-NMR (400.0 MHz. de-DMSO 8: 9.077 (8.4); 9.078 (8.4); 8.593 (4.1); 8.589 (4.2); 8.540 (3.1); 8.529 (3.2); 8.471 (8.5); 8.489 (8.4); 8.317 (0.7); 8.019 (4.1); 8.015 (4.0 .848 (1.5); 7.843 (5.5); 7.839 (7.4); 7.834 (5.9); 7.828 (4.6); 7.820 (2.2); 7.528 (5.7); 7.517 (1.0); 7.513 (0.9); 7.504 (5.1); 3.328 (238.4 3.109 (1.9); 3.091 (8.4); 3.072 (8.5); 3.054 (2.0); 2.874 (0.4); 2.864 (0.9); 2.854 (1.2); 2.848 (1.9); 2.838 (2.0); 2.827 (1.2); 2.818 (1.0; 2.808 (0.4); 2.878 (1.5); 2.871 (2.2); 2.667 (1.8); 2.882 (0.8); 2.525 (5.8); 2.520 (8.4); 2.511 (110.7); 2.507 (227.2); 2.502 (302.7); 2.498 (222.3); 2.493 (109.8); 2.338 (0.8); 2.334 (1.4); 2.329 (1.9); 2.324 (1.4); 2.320 (0.7); 1.398 (1.0); 1.235 (8.0); 1.217 (18.0); 1.198 (7.0); 0.738 (1.2); 0.723 (3.4); 0.718 (4.9); 0.708 (4.5); 0.700 (3.8); 0.688 (1.6); 0.577 (1.8); 0.588 (4.8); 0.580 (4.3); 0.558 (4.1); 0.550 (3.9); 0.538 (1.2); 0.146 (0.8); 0.008 (4.5); 0.000 (140.4); 0.009 (5.1); 0.150 (0.8) Example 1—73-157: 1H—NMR (400.0 MHz. 48011480): 8: 9.389 (0.4); 9.355 (9.8); 8.984 (5.4); 8.959 (5.4); 8.842 (0.5); 8.827 (9.7); 8.577 (4.7); 8.540 (3.8); 8.529 (3.8); 8.317 (1.2); 7.913 (12.3); 7.893 (4.1); 7.887 (2.8); 7.541 (4.9); 7.520 (4.4); 4.038 (0.9); 4.020 (0.8); 4.002 (0.4); 3.454 (0.4); 3.425 (0.9); 3.408 (2.4); 3.387 (2.9); 3.372 (3.7); 3.353 (5.7); 3.329 2.836 (2.3); 2.827 (1.6); 2.818 AA894.0); 2.952 (0.7); 2.934 (2.2); 2.915 (2.5); 2.900 (2.2); 2.882 (2.0); 2.884 (1.6); 2.855 (1.6); 2.848 1.1); 2.807 (0.5); 2.878 (3.2); 2.871 (4.1); 2.667 (3.2); 2.507 (482.3); 2.502 (589.8); 2.498 (442.8); 2.333 (2.8); 2.329 (3.8); 2.325 (2.8); 1.989 (3.4); 1.398 (1.9); 1.234 (0.7); 1.193 (1.0); 1.175 (1.8); 1.157 (0.9); 1.099 (7.8); 1.081 (18.0); 1.083 (7.3); 0.741 (1.3); 0.728 (4.0); 0.723 (5.4); 0.711 (5.1); 0.705 (4.3); 0.894 (1.7); 0.583 (1.8); 0.573 (5.5); 0.566 (5.3); 0.557 (4.5); 0.545 (1.3); 0.146 (0.3); 0.008 (3.2); 0.000 (83.8) Example l-T3—158: ‘H-NMR (400.0 MHz. 85-01430): 8: 9.234 (1.6); 9.229 (1.6); 9.185 (3.1); 8.632 (1.8); 8.827 (1.6); 8.584 (3.2); 8.547 (1.2); 8.536 (1.2); 7.875 (4.5); 7.871 (1.9); 7.857 (1.5); .852 (0.9); 7.548 (1.5); 7.543 (0.7); 7.529 (0.6); 7.525 (1.4); 4.151 (0.7); 4.132 (2.2); 4.114 (2.2); 4.095 (0.7); 3.329 (71.4); 2.887 (0.3); 2.857 (0.4); 2.849 (0.7); 2.839 (0.7); 2.830 (0.5); 2.821 (0.3); 2.878 (0.4); 2.672 (0.8); 2.887 (0.4); 2.525 (1.6); 2.511 (33.5); 2.507 (88.9); 2.502 (87.7); 2.498 (84.8); 2.494 (32.5); 2.334 (0.4); 2.329 (0.8); 2.325 (0.4); 1.398 (18.0); 1.324 (2.8); 1.308 (5.7); 1.287 (2.6); 1.238 (0.3); 0.738 (0.4); 0.725 (1.3); 0.720 (1.8); 0.708 (1.8); 0.702 (1.4); 0.891 (0.8); 0.580 (0.8); 0.589 (1.8); 0.583 (1.6); 0.554 (1.4); 0.541 (0.4); 0.008 (0.4); 0.000 ; "0.008 (0.4) Example I-T3-159: 1H-NMR (400.0 MHz. ds—DMSO): 8: 9.812 (2.8); 9.173 (7.1); 8.904 (2.9); 8.880 (0.5); 8.874 (0.4); 8.852 (1.7); 8.845 (2.6); 8.822 (6.9); 8.816 (7.2); 8.765 (9.2); 8.566 (0.7); 8.554 (1.9); 8.512 (5.8); 8.484 (11.2); 8.455 (6.7); 8.449 (6.6); 8.318 (0.7); 8.263 (1.1); 8.257 (1.1); 8.237 (0.4); 8.093 (5.7); 3.903 (16.0); 3.680 (2.8); 3.593 (0.6); 3.582 (0.9); 3.570 (0.7); 3.388 (0.9); 3.333 (306.9); 3.276 (1.0); 3.267 (1.3); 3.168 (13.0); 3.044 (0.4); 2.980 (0.9); 2.891 (2.0); 2.732 (1.7); 2.676 (1.9); 2.672 (2.6); 2.667 (1.9); 2.542 (0.9); 2.525 (6.2); 2.511 (158.8); 2.507 (322.0); 2.503 (423.2); 2.498 AA311.3); 2.494 (156.1); 2.334 (2.0); 2.329 (2.7); 2.325 (2.1); 2.083 (0.4); 2.065 (0.3); 1.877 (2.4); 1.867 (5.7); 1.857 (6.2); 1.848 (2.6); 1.7180.4); 1.709 (0.4); 1.435 (0.4); 1.355 (0.6); 1.298 (0.6); 1.284 (0.5); 1.276 (0.6); 1.259 (3.3); 1.249 (6.9); 1.239 (9.7); 1.236 (9.6); 1.001 (0.6); 0.991 (0.5); 0.986 (0.5); 0.871 (0.5); 0.862 (0.6); 0.854 (1 .3); 0.843 (0.5); 0.837 (0.7); 0.827 (0.3); 0.008 (0.7); 0.000 (25.7); 30.008 11-0) Example 1-T3-160; 1H-NMR (400.0 MHz. CDSCN): 8: 8.728 (0.3); 8.722 (0.5); 8.704 (9.5); 8.698 (9.6); 8.524 (0.3); 8.353 (7.7); 8.234 (15.1); 8.219 (12.8); 8.100 (7.8); 8.052 (10.3); 8.046 (10.1); 7.603 (0.4); 7.592 (0.6); 7.560 (0.5); 7.537 (0.5); 7.495 (0.5); 7.490 (0.5); 7.342 (0.5); 7.067 (2.6); 5.449 (0.7); 4.054 (1.4); 3.893 (0.3); 3.441 (0.7); 3.375 (0.6); 3.241 (1.1); 3.154 (3.0); 3.070 (0.6); 2.886 (0.9); 2.876 (1.9); 2.867 (2.7); 2.858 (3.9); 2.849 (3.9); 2.840 (2.7); 2.831 (1.9); 2.821 (0.7); 2.600 (0.3); 2.590 (0.4); 2.531 (0.4); 2.470 (3.6); 2.465 (5.0); 2.460 (3.7); 2.432 (0.3); 2.425 (0.4); 2.394 (0.4); 2.368 (0.5); 2.359 (0.5); 2.329 (0.6); 2.316 (0.6); 2.289 (0.8); 2.261 (1.3); 2.257 (1.3); 2.255 (1.3); 2.243 (1.9); 2.178 (1072.5); 2.127 (0.9); 2.121 (1.9); 2.114 (3.1); 2.108 (4.0); 2.102 (2.8); 2 096 (1.6); 2.087 (0.7); 2.057 (0.4); 2.036 (0.7); 2.017 (1.1); 1.998 (1.2); 1.965 (20.5); 1.959 (52.5); 1.953 (270.7); 1.947 (487.5); 1.941 (851.8); 1.935 (450.7); 1.929 (234.0); 1.782 (1.4); 1.775 (2.7); 1.789 (3.8 )2 1.783 (2.5); 1.7757 (1.3); 1.711(24);_1.384 (0.4); 1.380 (0.8); 1.269(160); 0.897 (0.7); 0.881 (1 8); 0.884 (0.9); 0.808 (2.2); 0.795 (8.8); 0.790 ‘WO MRS/067647 — (q .1; u. l (8.9); 0.778 (9.1); 0.772 (6.9); 0.760 (3.0); 0.738 (0.4); 0.721 (0.4); 0.661 (0 4); 0.651 (0.4); 0.621 (3 0); 0.609 (81); 0.603 (8.3); 0599| (7.4); 0.594 (7.1); 0.581 (2.1); 0.543 (0.5); 0.390 (0.4); 0.365 (0.5); 0.146 (8.5); 0.085 (0.4); 0.078 (0.5); 0.065 (0.5); 0.008 (68.5); 0, 0 (1708.3); 0.009 (75 1); 0.049 (0.5); 0.058 (0.4); 0.150 (8.4) Example l-T3-161: 1H-NMR (400.0 MHz. CD3CN): 8: 8.626 (2.2); 8.153 (1.1); 8.140 ; 8.100 (13.1); 7.994 (7.6); 7.949 (7.7); 7.629 (9.3); 7.624 (11.5); 7.596 (6.2); 7.591 (4.8); 7.585 (2.3); 7.575 (7.4); 7.570 (6.0); 7.488 (0.5); 7.467 (0.4); 7.436 (11.0); 7.415 (8.4); 4.085 (1.8); 4.068 (5.5): 4.050 (5.6); 4.032 (1.9); (0.7); 3.425 (1.5); 3.416 (1.9); 3.407 (8.0); 3.394 (2.9); 3.383 (1.8); 3.376 (1.3); 3.365 (0.6); 3.033 (0.5); 2.905 (0.4); 2.683 (0.6); 2.865 (0.6); 2.467 (0.8); 2.143 (2313.8); 2.117 (49.9); 2.108 (11.0); 2.101 (6.8); 2.095 (3.7); 1.972 (32.2); 1.964 (49.2); 1.958 (118.9); 1.953 (611.9); 1.946 9); 1940 (1474.5); 1.934 (1019.6); 1928 (525.2); 1.781 (2.8); 1.775 (5.7); 1.769 (7.9); 1.762 (5.4); 1.756 (2.4); 1.437 (7.6); 1.270 (1.1); 1.222 (6.5); 1.204 (13.0); 1.186 (6.4); 0.951 (2.0); 0.939 (6.4); 0.934 (8.6); 0.921 (8.9); 0.915 (6.5); 0.902 (2.8); 0.881 (0.8); 0.863 (0.6); 0.821 (0.5); 0.811 (0.4); 0.782 (2.8); 0.770 (7.8); 0.764 (8.1); 0.760 (6.9); 0.754 (6.8); 0.741 (1.9); 0.192 (0.4); 0.146 (19.2); 0.087 (1.0); 0.063 (1.5); 0.008 (155.4); 0.000 (3971.4); 0.009 (173.7); 0.068 (0.4); 0.150 (18.8) Example l-T3-162: 1H-NMR (400.0 MHz. CD3CN): 6: 8.194 (6.9); 8.179 (6.7); 7.972 (3.4); 7.759 (3.0); 7.688 (3.5); 7.682 (4.6); 7.655 (2.4); 7.650 (1.8): 7.635 (2.7); 7.629 (2.4); 7.477 (4.3): .456 (3.4); 6.951 (1.1); 2.872 (0.7); 2.862 (1.1); 2.854 (1.6); 2.844 (1.6); 2.835 (1.1); 2.826 (0.8); 2.471 (0.3); 2.466 (0.5): 2.461 (0.3); 2.180 (199.2); 2.134 (0.5); 2.115 (0.5); 2.109 (0.6); 2.102 (0.4); 1.965 (2.7); 1.959 (6.7); 1.953 (37.6); 1.947 (69.0); 1.941 (93.6); 1.935 (65.6); 1.929 (34.4); 1.776 (0.4); 1.770 (0.5); 1.763 (0.4); 1.437 (16.0); 1.269 (0.4); 0.795 (0.9); 0.782 (2.6); 0.777 (3.6); 0.765 (3.7); 0.75 (2.8); 0.747 (1.2); 0.612 (1.2); 0.601 (3.3); 0.595 (3.4); 0.591 (3.1); 0.586 (3.0); 0.573 (0.9); 0.146 (1.5); 0.008 (10.7); 0.000 (294.5); -O.150 (1.5) Example I-T3-163: 1H-NMR (400.0 MHz. CD3CN): 8: 8.205 (4.0); 8.190 (4.1); 7.973 (2.2); 7.760 (2.0); 7.736 (2.0); 7.731 (2.6); 7.704 (1.2); 7.700 (1.0); 7.684 (1.4); 7.679 (1.2); 7.600 (0.8); 7.509 (2.3); 7.488 (1.9); 2.161 (116.4); 2.121 (0.5); 2.114 (0.5); 2.108 (0.6); 2.102 (0.4); 1.963 (2.5); 1.952 (29.4); 1.946 (52.9); 1.941 (70.8); 1.934 (50.0); 1.928 (26.6); 1.769 (0.4); 1.598 (1.0); 1.583 (2.9); 1.576 (2.8); 1.563 (1.3); 1.436 (16.0); 1.362 (1.3); 1.348 (2.9); 1.341 (3.0); 1.327 (1.0); 1.269 (0.5); 0.145 (1.2); 0.000 (226.5); —0.150 (1.2) Example 64: ‘H-NMR (400.0 MHz. du-DMSO): 8: 9.460 (5.0); 8.854 (7.4); 8.671 (4.0); 8.651 (4.0); 8.535 (7.4); 7.846 (1.3); 7.840 (3.0); 7.833 (4.3); 7.827 (5.4); 7.824 (4.4); 7.818 (1.5); 7.594 (4.1); 7.584 (0.8); 7.582 (0.8); 7.572 (3.6); 4.056 (1.2); 4.038 (3.7); 4.020 (3.7); 4.002 (1.3); 3.934 (1.6); 3.329 (39.1); 2.671 (0.4): 2.525 (1 .1); 2.507 ; 2.502 (56.3); 2.498 ; 2.329 (0.4); 1.989 (16.0); 1.619 (1.7); 1.605 (4.3); 1.598 (4.6); 1.585 (1.9); 1.397 (5.6); 1.295 (2.0); 1.281 (4.2); 1.275 (4.5); 1.260 (1.6); 1.193 (4.2); 1.175 (8.4); 1.157 (4.1); 1.069 (10.8); 0.008 (1.8); 0.000 (48.4); -0.008 (2.3) Example I-T3-165: 1H—NMR (400.0 MHz. CD3CN): : 8.748 (1.7); 8.742 (1.8); 8.353 (1.5); 8.243 (2.8); 8.228 (2.4); 8.116 (1.9); 8.110 (2.1); 8.101 (1.5); 7.706 (0.5); 3.236 (0.9); 3.070 (0.4); .883 (0.4); 2.284 (0.3); 2.154 (118.3); 2.120 (0.8); 2.114 (0.9); 2.108 (0.9); 2.102 (0.7); 2.095 (0.4); 1.972 (0.7); 1.965 (3.4); 1.956 (8.8); 1.953 (47.0); 1.946 (85.3); 1.940 (114.8); 1.934 ; 1.928 (41.8); 1.775 (0.5); 1.769 (0.7); 1.763 (0.5); 1.612 (0.8); 1.597 (2.0); 1.591 (2.0); 1.577 (1.0); 1.437 (16.0); 1.370 (1.0); 1.356 (2.0); 1.349 (2.1); 1.334 (0.8); 1.269 (0.9); 0.146 (1.9); 0.008 ; 0.000 (390.9); — 0.009 (19.9); 0.150 (2.0) Example l-T3-166: 1H-NMR (400.0 MHz. ds-DMSO): 8: 9.440 (11.8); 9.127 (15.9); 8.569 (7.7); 8.491 (16.0); 8.318 (2.5); 7.965 (7.6); 7.961 (7.7); 7.926 (7.5); 7.921 (12.0); 7.912 (6.7); 7.906 A3.4); 7.891 (6.2); 7.885 (4.8); 7.573 (10.1); 7.553 (9.2); 3.459 (0.4); 3.399 (0.7); 3.365 (1.8); 3.331 (1516.7); 3.298 (1.6); 2.701 (0.4); 2.694 (0.3); 2.676 (6.5); 2.671 (9.1); 2.667 (6.9); 2.638 (0.4); 2.576 (1.1); 2.529 (53.9); 2.520 (35.9); 2.511 (509.9); 2.507 (1041.6); 2.502 (1375.8); 2.498 (1016.8); 2.417 (0.5); 2.351 (0.6); 2.334 (6.6); 2.329 (9.1); 2.325 (6.8); 2.302 (0.3); 1.621 (3.9); 1.607 (9.8); 1.600 (10.6); 1.587 (4.4); 1.547 (0.4); 1.348 (0.4); 1.307 (4.5); 1.294 (9.7); 1.287 (10.6); 1.273 (3.7); 1.237 (0.4); 0.146 (3.4); 0.024 (0.3); 0.008 (24.7); 0.000 (766.8); 0.008 ; 0.032 (0.8); 0.150 (3.5) Example 67: 11101le (400.0 MHz. 68-01130): 8: 9.440 (6.2); 9.103 (8.3); 9.094 (0.8); 6.587 (4.2); 8.479 (8.5); 8.317 (1.1); 8.021 (4.5); 7.917 (3.9); 7.911 (6.2); 7.903 (3.6); 7.898 (1.8); 7.882 (3.2); 7.877 (2.5); 7.597 (0.4); 7.574 (5.4); 7.554 (4.7); 3.329 (494.7); 3.110 (1.9); 3.092 (6.3); 3.074 (6.4); 3.056 (2.0); 2.871 (0.3); 2.676 (3.0); 2.671 (4.2); 2.667 (3.1); 2.524 (9.6); 2.507 (478.6); 2.502 (637.0); 2.498 ); 2.408 (0.8); 2.333 (2.9); 2.329 (4.1); 2.325 (3.1); 1.621 (2.0); 1.607 (5.2); 1.600 (5.6); 1.587 (2.3); 1.306 (2.4); 1.293 (5.3); 1.286 (5.7); 1.272 (2.1); 1.261 (0.6); 1.235 (7.6); 1.217 (16.0); 1.199 (7.1); 0.146 (1.6); 0.008 (11.5); 0.000 (362.6); 0.008 (14.5); 0.026 (0.6); 0.150 (1.6) Example I-T3—168: 'H-NMR (400.0 MHz. 1180111180); 6: 8.917 (4.0); 8.676 (2.2); 8.612 (2.2); 8.554 (1.4); 8.543 (1.4); 8.439 (4.1); 7.783 (0.8); 7.777 (1.6); 7.770 (2.3); 7.764 (3.0); 7.539 (2.1); 7.527 (0.4); 7.517 (1.8); 4.038 (0.4); 4.020 (0.4); 3.936 (2.3); 3.333 ; 2.864 (0.4); 2.854 (0.6); 2.846 (0.8); 2.836 (0.8); 2.827 (0.6); 2.818 (0.4); 2.507 (26.6); 2.503 (34.6); 2.498 (26.4); 1.989 (1.7); 1.296 (0.7); 1.193 (0.5); 1.175(0.9);1.157(0.5); 1.069 (16.0); 0.733 (0.5); 0.720 (1.6); 0.716 (2.1); 0.703 (2.0); 0.698 (1.8); 0.686 (0.7); 0.566 (0.7); 0.555 (2.1); 0.549 (2.0); 0.540 (1.8); 0.527 (0.6); 0.000 (11.0) Example I-T3-169: 1H-NMR (400.0 MHz. da—DMSO): : 9.461 (11.1); 9.416 (0.4); 8.936 (15.7); 8.681 (8.8); 8.616 (8.7); 8.450 (16.0); 7.833 (11.0); 7.827 (9.7); 7.820 (7.2); 7.652 (0.3); 7.589 (8.1); 7.578 (1.9); 7.567 (7.0); 7.556 (0.5); 4.038 (0.8); 4.020 (0.8); 3.937 (0.6); 3.333 (133.2); 2.672 (0.7); 2.503 ); 2.330 (0.7); 1.989 (3.2); 1.622 (3.6); 1.607 (9.7); 1.601 (10.5); 1.587 (4.3); 1.563 (0.4); 1.556 (0.4); 1.547 (0.5); 1.334 (0.4); 1.314 (0.5); 1.300 (4.8); 1.294 (5.2); 1.281 (9.9); 1.274 (10.4); 1.259 (3.7); 1.235 (0.6); 1.193 (0.9); 1.175 (1.7); 1.157 (0.9); 1.069 (3.7); 0.000 (35.7) Example l-T3-170: 1H-NMR (400.0 MHz. de-DMSO) 8: 9.441 (1.5); 9.436 (2.4); 8.694 (1.7); 8.619 (3.2); 8.443 (1.7); 8.398 (3.2); 8.274 (2.8); 7.960 (1.6); 7.956 (1.6); 7.810 (0.9); 7.804 (2.1) 7.797 (2.3); 7.792 (2.9); 7.787 (3.1); 7.782 (0.9); 7.742 (1.6); 7.739 (1.6); 7.569 (1.0); 7.557 (2.1); 7.546 (1.3); 7.535 (1.8); 4.056 (1.2) 4.038 (3.6); 4.020 (3.7); 4.002 (1.2); 3.332 (35.6); 3.116 (0.7); 3.097 (2.3); 3.079 (2.4); 3.061 (0.7); 2.525 (0.5); 2.512 (10.5); 2.507 (21.4), 2.503 (28.1); 2.498 (20.5); 2.494 (9.9); 1.990 (16.0); 1.615 (1.1); 1.601 (2.8); 1.594 (2.9); 1.581 (1.3); 1.289 (1.3); 1.276 (2.8); 1.269 (3.0); 1.255 (1.1); 1.208 (2.7); 1.193 (5.6); 1.190 (6.2); 1.175 (9.2); 1.157 (4.2); 0.000 (3.5) Example l—T3—17111H—NMR (400.0 MHz. do-DMSO): 8: 9.443 (12.6); 9.162 ; 8.676 (8.2); 8.530 (16.0); 8.412 (7.8); 8.317 (4.0); 7.937 (8.0); 7.932 (12.0); 7.921 (6.8); 7.915 (3.8); 7.900 (6.4); 7.895 (5.0); 7.716 (0.4); 7.584 (10.3); 7.563 (9.1); 4.358 (2.5); 4.332 (7.5); 4.306 (7.8); 4.280 (2.7); 4.104 (0.5); 4.079 (0.4); 3.496 (0.5); 3.460 (0.4); 3.466 (0.5); 3.452 (0.4); 3.396 (0.8); 3.329 (1554.1); 3.287 (1.0);_2.676 (8.0); 2.671 (11.1); 2.667 (86); 2.645 (0.6); 2.525 V170- 2015/067647 — 246 - PCT/EPZOM/WS795 (23 7). 2.511 (314.7); 2.507 (1233 3). 3371); 2.493 (1234.4); 2 339 (0.3);27330 (0.3); 2.333 (7.3); 2.329 (11.0); 2.325 (3.3); 2.253 (0. 4) 1.4) 1323 (40) 1303(10 0) 1.301 (103) 1533 (4 3) 1543 (0 5) 1.347 (0.4); 1.303 (4 7); 1.293(100); 1.233(10 3); 1.272; (:19); 1234(0 7) 0143 (0 5) 0.017 (04).300313 .11); 0000(1151); 0.003 —0.150 (0.3) Example 1T3172: 1HNMR (400.0 MHz. (1.1-011130): 3: 3313(03) 3593 (34) 3529 (2.9);3513 (3.0); 3.492 (0.7); 3.331 (3.5); 3.333 (0.3); 7.953 (4.4); 7.953 (4.4); 7.749 (2.3); 7.743 (4.3); 7.739 (5.0); 7.725 (13.2); 7.507 (4.3); 7.433 (2.3); 7.435 (3.1); 4.055 (1.2); 4.033 (3.3); 4.023 (3.7); 4.002 (1.2); 3.329 (51.5); 3.112 (1.9); 3.094 (3.1); 3.373 (3.1); 3.057 (2.0); 3.043 (0.4); 3.029 (0.9); 3.311 (0.9); 2.353 (0.3); 2.347 (1.1); 2.333 (1.3); 2.323 (1.3); 2.319 (1.1); 2.309 (0.9); 2.373 (3.4); 2.371 (0.5); 2.337 (0.4); 2.524 (1.3); 2.511 (30.4); 2.507 (33.9); 2.502 (79.7); 2.493 (53.7); 2.494 (29.4); 2.333 (0.4); 2.329 (0.5); 2.324 (0.4); 1.939 (13.0); 1.235 (0.4); 1.207 (3.3); 1.192 (7.1); 1.139 (14.7); 1.175 (13.4); 1.170 (7.2); 1.157 (4.7); 1.033 (0.4); 0.727 (1.1); 0.714 (3.3); 0.709 (4.3); 0.397 (4.3); 0.391 (3.7); 0.330 (1.5); 0.533 (1.5); 0.552 (4.3); 0.543 (4.3); 0.533 (3.3); 0.524 (1 .1); 0.003 (2.2); 0.000 (31.3); 3.003 (2.4) Example l-T3-173: 1H—NMR (400.0 MHz. de-DMSO); : 8.653 (6.0); 8.567 (3.1); 8.561 (3.2); 8.401 (5.7); 8.091 (10.1); 8.013 (3.1); 8.007 (3.2); 7.957 (0.4); 6.579 (0.7); 5.409 (0.3); 3.923 (16.0); 3.592 (0.3); 3.367 (923.7); 2.985 (14.3); 2.767 (0.4); 2.740 (1.3); 2.725 (0.9); 2.704 (1.4); 2.674 (0.9); 2.509 (96.0); 2.505 (123.6); 2.501 (91.6); 2.332 (0.8); 2.074 (1.6); 1.271 (0.8); 1.169 (5.1); 0.467 (4.5); 0.450 (2.4); 0.008 (1.4); 0.000 (28.9) Example 741. 1H-NMR (400.0 MHz. 31—01430): 3: 3335 (75) 3372 (33) 3339 (4 0) 3350 (39) 3349 (39) 3345 (29) 3553 (2 5) 3545 (2 5) 3525 (73) 7737 (17); 7.731 (29); 7733 (4.0); 7733 (113); 7.543 (32) 7542 (17.); 7527 (15); 7524 (23) 4053 (12); 4.033 (33) 4020 (37); 4002 (1. 2); 3329 (59 3). 2335 (07) 2353 (09) 2347 (14) 2333 (15); 2323 (09) 2.313(07);2371(3.;4) 2525 (10;.) 2520 (1 .3;) 2.511 (21. 0); 2507(423); 2502 (537) 2493(41. 2); 2493(193) 2329 (04) 1939 (130) 3) 1175 (37) 1157 (42) 0.7.33(10); 0720 (27) 0.7.15(33); 0.703 (3.5); 0.397 (2.9); 0.333 (1.3); 0.533 (1.3); 0.555 (3.7); 0.549 (3.3); 0.545 (3.1); 0.540 (3.0); 3.527 (0.9); 0.003 (1.4); 0.000 (40.4); - 0.009(13) Example |-T3- 175: 1H—NMR (400.0 MHz. CD3CN): 6: 8.146 (3.1); 8.082 (4. 8); 7.714 (1.6); 7.697 (2.0); 7.692 (2. 5); 7.663 (1. 3); 7.658 (1.0); 7.642 (1.5); 7.637 (1.3); 7.472 (2.3); 7.451 (1.8); 6. 931 (0. 6); 2.873 (0. 4); 2. 864 (0.6); 2.855 (0.9); 2.845 (0.9); 2. 837 (0. 6). 2. 827 (0.4); 2.165 (79.0); 2.115 (O. 4); 2.108 (0.5); 2.102 (0.3); 1.965 (1.5); 1.959 (4.0); 1.953 (28.1); 1.947 (52.6); 1.941 (72.5); 1.935 ; 1.929 (26.2); 1.769 (0.4); 1 .437 (160;) 0.796 (0. 5); 0.783 (1.5); 0.778 (2.0); 0.765 (2.0); 0.760 (1.5); 0.748 (0.7); 0.613 (0.6); 0.601 (1.7); 0.595 (1.8); 0.591 (1.6); 0.586 (1. 6); 0.574 (0. 5); 0. 000 (0-6) Example l-T3-176: 1H-NMR (400.0 MHz. CDSCN): 8: 19.983 (0. 4); 8.920 (0.7); 8. 270 (0. 3); 8.158 (11.0); 8.124 (0.4); 8.095 (11.8); 8.083 (6.1); 8.035 (0.7); 7.746 (6.2); 7.741 (78); 7.713 (9.;2) 7392 (43) 7333 (44) 7.339 (33) 7.590 (03) 7535 (39) 7434 (57) 3901 (3.;1) 2470 (25) 2433 (34) 2.431 (2.;3) 2.417 (1.) 2179 (17019) 2153 (399) 2.121 (2.;3) 2.115(33). 2109 (43) 2103 (32) 2093 (19) 2034 (05) 1935 (12 0) 1954 (2135) 1947 (401 .4;) 1.941 (5435;) 1935 (334.1); 1.929 (201.2); 1.732 (1.3); 1.773 (2.3); 1.770 (3.4) 1734 (25) 1599 (31) 1.534(3.5) 1.577 1.534(.1); 1524 (37) 1.437 (13.0); 1.401 (0.7); 1.332 (3.9); 1.349 (3.3); 1.342 (3.3); 1327 (31) 1233 (27) 0.332(0.4): 0.030 (42) Example l-T3-177: 1H-NMR (400.0 MHz. de-DMSO): : 9.462 (7.5); 8.855 (1.9); 8.790 (8.8); 8.673 (1.1); 8.653 (1. 1); 8.536 (1. 9); 8. 483 (8.9); 8.391 (4.5); 8.388 (4.6); 8.105 (4.5); 8.102 (4.5); 7.846 (0.5); 7.840 (1.0); 7.833 (2.8); 7.827 (5.2); 7.820 (5.9); 7.814 (7. 0); 7. 810 (5.4); 7.804 (1.9); 7.595 (1.3); 7.5865(5. 5); 7. 573 (1. 8). 7.564 (4.6); 4.055 (0.5); 4.038 (1.4); 4.020 (1.4); 4.002 (0.5); 3.331 (91.4); 3.168 (2.0); 3.150 (6.5); 3.131 (6.6); 3.113 (2.O); 2.676 (05); 2.672 (0.7); 2.667 (0.5); 2.525 (1.8); 2.511 (39.2); 2.507 (78.6); 2.502 (103.0); 2.498 (76.1); 2.494 (38.1); 2.334 (0.5); 2.329 (0.7). 2.325 (0.5); 1.989 (6.1); 1.619 (2.5); 1.604 (6.3); 1.598 (6.8); 1.585 (2.8); 1.397 (5.9); 1.293 (2.9); 1.279 (6.3); 1.273 (6.7); 1. 258 (2. 4); 1.203 (7.5); 1.193 (2.5); 1.184 (16.0); 1.175 (4.1); 1.166 (7.2); 1.157 (2.0); 1.069 (0.5); 0.008 (2.2); 0.000 (62.2); -0.008 (2.5) e I-T3-178z1H-NMR (400.0 MHz. 1153111130); 3: 3.730 (5.4); 3.723 (5.4); 3.701 (10.4); 3.553 (3.7); 3.545 (3.7); 3.433 (0.5); 3.433 ; 3.313 (0.3); 3.233 (5.5); 3.234 (5.4); 7.730 (24). 7754 (33) 7733 (143) 7524 (45) 7505 (23) 7502 (33) 4055(12) 4037 (33) 4.03.20() 4002() 3430() 3442 (5.;0) 3424 (50) 3.1.;405(17) 3329 (1243) 2333 (04) 2353 (10) 2343 (14) 2340 (22) 2333 (22) 2.321 (14) 2.311 (10) 2.302 (0.;4) 2375 (11); 2.371 (1.;5) 2337 (12) 2.541 (33) 2503 (1754) 2502 (2233) 2493 (1371) 2333 (11); 2329 (14) 2324 (11); 1939 (157) 1235 (04) 1193 (4 2) 1175 (33) 1157 (51) 1150 (75) 1..;132(130) 1.113(72); 0723 (14) 0.715(42); 0710(55) 0.393 (5.2) 0.392 (4.4); 0.331 (1 .7); 0.531 (1.3); 0.551 (5.3); 0.545 (5.4); 0.535 (4.3); 0.523 (1.3); 0.143 (0.4); 0.000 (94.7); 3.003 (4.3);. 0.150 (0.4) Example 133-179: ‘H—NMR (400.0 MHZ. ds-DMSO): 3:11.332 (95) 3.701 (04) 3543 (3 2) 3537 (32) 3504 (04) 3437(100) 3432 (5.1); 3.477 (4.7) 3433 (04) 3.317(14); 3095 (43) 3.091 (4.3); 7739 (21) 7734 (3 9) 7753 (5 3) 7743 (115) 7733 (07) 7540 (5.3); 7.533 (1.3) 7524 (13); 7517(4. 5); 4.055(1.0); 4.337 (3.2) 4.320(3. 2); 4002(1.1); 3507 (03). 3443 (0.4); 3.424 (0.4); 3.393 (0.5); 3.373 (0.3); 3.332 (779.0); 3.293 (07); 3.031 (3. 3); 3.042 (1.3); 3.024 (2 ); 3.003 (2 2) 2.995(0 5.) 2.990 (2.0); 2.971 (0.3); 2.370 (0.4); 2.330 (3.9); 2.350 (1.3); 2.342 (2 0); 2.331 (2.;1) 2.322 (1.3); 2.313 (10); 2.303 (0.4) 2.1330( .3); 2.373 (2.7); 2.371(3.7) 2.337 (23); 2.534 (1.0); 2.535 (2.3); 2.547 (3. 3); 2542 (53) 2.525 (110.3); 2.523(1 5.4) 2511 (2050) 2507 (417.5); 2.502 (550.3); 2493 (4035) 2493 (1932;) 2333 (2 3) 2.329 (33) 2325 (27) 1.939(1.;133) 1293(0 3.); 1259 (05) 1235 (09) 1193 (3.9);1.175 (73) 1.157 (33) 1132 (03) 1047 (72) 1..029(130); (39); 0733 (1. 3) 0720 (3.5;) 3.715 (5.2); 0.703 (4.7) 0397 (4.1); 0.335 (1.7) 0.533 (1. 7); 3552 (5.0); 0543 (47) 0.542 (44); 0.533 (4.2); 0.524 (13.); 0. 143 (1. 1); 0.003 (3.3); 0.000 (231.7I); 0.009 (10.3); 3.150 (1.1) e 1—13—130: 1H-NMR (400.0 MHz. (16317130): 3: 9.105 (5.5); 9.100 (4.5); 3.339 (0.7); 3.371 (9.2); 3.531 (4.3); 3.570 (3. 0); 3. 534 (3.3); 3.559 (5.5); 3.545 (9.1); 3.317 (0.9); 7.317 (0.3); 7.312 (0.3); 7.774 (3.3); 7.733 (4.2); 7.755 (7.5); 7.751 (13.2); 7.553 (4.7) 7.543 (21); 7.535 (2.4); 7.530 (3.5); 4.055 (0.3); 4.037 (2.1); 4.020 (2.1); 4.002 (0.7); 3.559 (2.3); 3.541 (3.5); 3.523 (3.4); 3.504 (2.1); 3. 334 (39.2) 3.323 ); 2.333 (1.3); 2353 (1. 3); 2347 (2. 5); 2337 (2.3); 2.329 (1.5); 2.319 (1.0); 2.309 (0.4); 2.373 (2.3); 2.371 (2 .5); 2337 (1. 3) 2.321 (0.4); 2.507 (343.0); 2.502 (330.;1) 2.493 ); 2.333 (2.1); 2.329 (24); 2.324 (1.3); 1.995 (23); 1.939 (3.7); 11.293 (0.4); 1.253 (0.3); 11.249 (0.7); 1.233 (1 2.) 1.193 (3.3) 1.131 (3.3); 1.175 (7.3); 1.133 (13.0); 11.157 (4.7); 1.144 (3.3); 1.114 (0.3); 0.731 (1.9); 0.719 (5.2); 0.714 (5.7); 0.702 (5.3); 0.393 (4.2); 0.334 (1.3), 3.593 (0.3); 0.533 (2.7); 0.553 (3.7); 0.547 (3.1); 0.533 (4.5); 0.525 (1.3); 0.003 (15.3); 3.000 (31.3); 3.003 (2.7) V10 13713.47 - 247 — PCT/EPZGM/073795 131311111113l—T3—181:1H—NIV1R (400. 0 MHZ. O): 8: 9.108 (0.4); 9.087 (10.3); 8.892 (5.1); 8.888 (5.2); 8.613 (0.4); 8.591 (10.7); 8579 (3. 8); 8. 568 (3. 7); 8. 407 (5. 3); 8. 403 (5. 3;) 7 787 (2 0.); 7 781 (4. 5); 7.775 (6.6); 7.769 (7.7); 7.765 (6.0); 7.759 (2.3); 7.575 (6.0); 7. 564 (1. 5); 7552 (5. 0); 4. 056 (1.1); 4. 038 (3. 4); 41. 020 (34) 4.002 (1. 2); 3.330 (39.4); 3.101 (0. 5); 3.083 (1.8); 3.065 (2.2): 3.049 (2.3); 3.031 (21;) 3.012 (0 6); 2. 879 (0.4); 2. 869 (1. O); 2. 860 (1.) 2851 () 2841 (2.1;) 2833 (1. 4); 2.823 (1. 0); 2.813 (0.4); 2.676 (0.5); 2672 (0.;6) 2.667 (0.5); 2.601 (0.7) 2.583 (21') 25641 (2)2549 (2. 3); 2 530 (2.5); 2.525 (2.1); 2.507 (69.4); 2.503 (90.4); 2498 (68.1); 2.334 (0.4); 2.329 (0. 6); 2.325 (0. 4); 1.989 (14.7:.)1193 (39); 1.175 (7.7); 1.158 (38); 1.081 (O.4); 1.067 (7. 5); 1.048 (16.0); 1.030 (7. 2); 0.738 (1.3); 0.725 (4.0); 0.720 (5.5): 0.708 (5.1 ); 0.702 (4.4); 0.691 (18;) 0.566 (1 .:8) 0.555 (5.4): 0.549 (52); 0.539 (4.6); 0.527 (1.3); 0.008 (0.6); 0.000 (16.1) Example l—T3-182: 1H»NMR (4000.0 MHz. de-DMSO): (99.454 (7.2); 8.884 (10.2); 8.500 (10.2); 8.482 (49;) 8.478 (5.0); 8.317(04); 8.098 (5.0); 8.093(5. 0;) 7829 (15); 7.823 (5.9); 7.821 (7.8); 7.815(53); 7.807 (4.8); 7.801 (2.4); 7.588 (5.9;) 7.579 (1.0;) 7574 (1 .;0) 7.555 (51); 4.1055(. 2;) 4.038 (35) 4.020 (3.5); 4.002 (1.2); 3.329 ; 3.059 (0.5); 3.051 (1.8); 3.032(2 .1); 3017(2 3.) 2998 (21) 2.980 (05) 2575 (05); 2572 (08); 2557 (0.5); 2.594 (0.5); 2.575 (2.1); 2.557 (2.5); 2.541 (2.4); 2.523 (3 8;) 2520 (39;) 2.511 ) 2507 (931) 2503(1 22 1;)2.98 ) 2494 (440) 2.334 (0.8); 2.329 (0.8): 2.325 (0.5); 1.989 (158),122 (2.4). 1. 507 (59) 1.801 (5.4); 1588 (27) 1290 (28) 1275 (59); 1270 (54) 1.255 (2.4); 1.235 (0.5); 1.193 (4.2); 1.175 (8.3); 1.157(41); 1. 134 (0. 3); 1. 051 (7.3); 1.033 (15.0); 1.014 (7.1); 0.008 (0.8); 0.000 (23.5)- 0.008(09) Example I-T3-183: 1H-NMR (400.0 MHz. 116-01150); & 9.454 (4.5); 8.733 (3.3); 8.729 (3.5); 8.723 (5.9); 8.477 (5.5); 8.270 (3.3); 8.255 (3.3); 7.820 (1.3); 7.814 (3.0). 7.808 (4.3); 7.803 (4.8); 7.798 (3.7); 7.792 (1.4); 7.573 (4.0); 7.552 (0.9); 7.551 (3.4); 4.055 (1.2); 4.038 (3.5); 4.020 (3.7); 4.002 (1.2); 3.455 (0.9); 3.447 (2.9); 3.429 (3.0); 3.410 (1.0); 3.329 (48.5); 2.575 (0.4); 2.571 (0.5); 2.557 (0.5); 2.525 (1.5); 2.511 (35.4); 2.507 (71.4); 2.502 (93.1); 2.495 (58.1); 2.494 (33.4); 2.333 (0.4); 2.329 (0.5); 2.325 (0.4); 1.989 (15.0); 1.514 (1.5); 1.500 (3.9); 1.593 (4.1); 1.580 (1.7); 1.290 (19); 1.277 (4.0); 1.270 (4.3); 1.255 (1.5); 1.235 (0.5); 1.193 (4.4); 1.175 (8.8); 1.157 (4.9); 1.152 (5.1); 1.134 (10.7); 1.115 (4.8); 0.008 (0.5); 0.000 (19.5); 0.009 (0.7) Example I-T3-184: 1H—NMR (400.0 MHz. CDSCN): 8: 8.222 (1.1); 8.212 (14.6); 8.193 (0.9); 8.163 (0.7); 8.151 ; 8.150 (13.6); 7.984 (5.6); 7.968 (5.6); 7.937 (0.6); 7.860 (0. 5); 7.837 (0. 5): 7. 699 (87); 7. 694 (11.4); 7.666 (5.9); 7.660 (4.9); 7.645 (6.7); 7.639 (6.1); 7.588 (0.8); 7.523 (0.3); 7.480 (10.7); 7.459 (8.5; 6.928 (2.6;) 5.448 (5.4); 2.881 (0.7); 2.871 (1.9); 2.862 (2.7); 2.853 (4.3); 2.844 (4.3); 2.835 (2.8); 2.825 (2.1 ' (1. 8); 2. 464 (2.4 ); 2.460 (1.9); 2.455 (1.0); 2.293 (0.4); 2.270 (0.7); 2.266 (0.7); 2.246 (1.0); 2.227 (1.0); 2.160 ), 2.121 (33.;1 2.114 (4.2). 2.108 (5. 3); 2.102 (3.8); 2.096 (2.1); 2.036 (0.6); 2.018 (0.8); 1. 998 (0. 9); 1965 (197) 1.959 (49.7); 1.953 (311.9); 1. 9477575.9). 1.941 (7854-) 1. 935 (5489) 1929 (287.9); 1.883 (0.5); 1.782 (1.8) 1775 (34) 1759 (47) 1.73.53( 2;) 1757 (18) 1.525 (04 (0.3); 1.372(05); 1359 (04) 1.340 (1.4); 1.335 (0.8); 1.285 (2.9). 1.270 (15 0) 1.204 (0.3;) 0..918(04) 0899 (09) 0.882 (21; 0854 (1.1); 0.832(0 4.) 0795 (2.4); 0783 (71); 0.777 (97) 0755 (98) 0.750 (7.5) 0747 (33) 0725 (0.5); 0.708 (05) 0.552 (0.;5 0.543 (0.5); 0.527 (04;) 0.513 (33) 0.501 (8. 2) 0.5958); 1( 8;) 0.585(8- (7.8); 0.573 (23) 0.535 (0.3;) 0.520 (0.4); 0.478 (0.;3 0.392 .4): 0.387 (0.4); 0.008 (0.7): 0.000 (20.9); -0.009(1. 0) Example l—T3-185; ‘H-NMR (400.0 MHZ. CD3CN): :17.517(0.4);15.219(0.3);14973 (0)13920 (03) 8..;404(04) 8.0394( 4); 8224(15.0);8208 (08;..;)8155(129) 7985 (52) 797 (5.1); 7.938 (1.2); 7.884 (0. 5); 7840 (04); 7747 (78) 7741 (105) 7.715(5.2) 7710(43); 7.594 (50); 7589(5. 7;) 7.554 (35) 7524 (1.2); 7.501 (2.1;) 7.594(1. 3;) 7.590 (20) 7.554 (19); 7.541 (1. 1); 7.513 (95;) 7.492 (7.5); 7.292 (07) 7.0.282(4;) 7270 (0.7); 7.201 (0.4); 7.175 (1. 5) 7.158 (0. 4); 7.151 (04) 7.054 (0.5); 7.045 (0.4;) 5.914(0.4); 6.892 (0.4); 5.881 (08) 5.859 (0.5) 5.178 (03) 5.150 (0.4); 5.111 (0.4); 5.099 (04); 5.057 (04) 5.042 (0.4); 5.038 (0.4); 5.017 (0.4); 5.540 (0.4); 5.594 (03) 5.540 (03) 5.515 (0.4) 5485 (0.4); 5.427 (03) 5.373 (03) 4.507 (05) 4.491 (0.5); 4.058 (13;) 4.050 (1. 1); 4.032 (0.5); 3.789 (0.5); 3.775 (1. 0); 3.758 (2.9); 3.555 (0.4); 3.149 (04) 3.128 (0.4) 2.1720( 3.77;) 2.555 (05) 2.492(0 9); ( 8); 2.470 (5.1); 2.455 (9 0); 2.451 (5.7); 2.455 (3.4); 2.285 (0.4);2.254(0. 7); 2..247(1).2237 (11); 2.171 (2483.4) 2.1721( .1); 2.19.14( 5;) 2108 (11.9); 2.102 (88) 2095 (52) 2.075 (18;) 2.032 (09); 2.020 (0. 7) 2.0011(5) 1.972 (8.4;) 1.955 (395); 1.959 (102.1); 1.953 (5423) 1.947 (11998); 1.941 (1545.9); 1.935 (1157.;9) 1.929 (5191),.818(1.3);1782 (42); 1.775 (7.5); 1.759 (10.3); 1.753 (74);1.57 (45) 1.0722( .9); 1.708 (0.9); 1.595 (09); 1688 (09) 1.574(07);1.358 97 (48) 1583 (11.5);1575 (12.0);1552 (53),143 (08) 1.522(1.2);1.501 (0.5);1472 (05); 1437 (9.0); 1.402 (12),13 (5.2); 1348 (119) 1.341 (12.8);1.327 (7.5); 1.311 (35).159 (87) 1.21.22(9;) 1204 (32) 1185 (17); 1154 (0.5); 1.154 (05). 1.145 (05) 1.131 (05) 1109 (0.5); 1.095 (0.5); 1.091 1047 (0. 5); 1.040(04) 1.031 (0.4) 1009 (04) 0.987(04); 0.975 (04). 0952 (04) 0.945 (0 5) 0.897 (0.8); 0.881 (1.5); 0.855 (1.3); 0.3888(0. 9); 0.0.824( 5); 0806 (o5) 0.797 (0. 4); 0775 (0.4); 0.755(0.)0739 (04) 0535 (03) 0525 (0.3);0147 (0.4); 0.008 (2.5).0000 (802) 0.0020( 5;.) 0.121 (0.3); 0.149 (04); 0.213(04); -2.478 (03). 3017 (0. 3) Example 1T3185. 111—NMR (400.0 MHz. CDBCN); 8-8202 (80) 8190 (84) 7927 (07) 7858 (4 8) 7.731 (2.7); 7.708 7590 (4.8); 7.585 (5 ); 7.557 (28;) 7.2.552( 5;) 7537 (34) 7.532 (3.2); 7.590 (08) 7.477 (50) 7455 (40) 5.984 (03) 5.951 (1.9); 5.041 (0.3); 5.521 (0.4) 5.491 (0.4) 5.0455(3); 3.874 (09) 3.055 (0. 3) 2890 (45) 2.872 (10); 2853 (1.5); 2.853 (21) 2844 (2.2); 2.835 (1.7); 2.825 (1.1); 2799 (0.4) 2772(4.2); 270.11(4); 2.584(0. 4); 2.571 (0.4;) 2552 (04) 4); 2.501 (1.1); 2583 (04) 2543 (05) 2522 (05) 2505 (05) 455 (53) 2.351 (0.;9) 2.310(1.).2298 (13) 2179 (23772) 2.121 (5.;5) 2115 (53) 2108 (71;) 2102 (55) 2.430 (0. 8);2 .01.18( 0); 1953 (3449) 1947 (523.;4) 1.91.841 (8407) 1935 (5413); 1929 (3742) 1827 (05); 1.781 (2.;1) 1775 (35) 1.4770( ); 1753 (35); 1.758 (2 2) 1437 (150) (4); 1283 (0 5) 1268 (09) 0794 (1.2) 0777 (51) 0754 (5.1); 0.747 (1.8); 0.738(4) 0.512(15) 0.00 (49) 0594 (53) 0586 (4.91' 0.573 (1.5); 0.000 (28.5) Example 1-T3—187. 1H—NMR (400.0 MHz. CDSCN): 8: 19.987 (0. 6); 8.214 (12.6); 8.200 (13.9); 7.859 (6.8); 7.738 (9.0); 7.733 (14.7); 7.707 (9.2); 7.701 (5.6); 7.686 (6.6); 7.680 (5.9); 7.610 (3.2); 7.587 (1.7); 7.510 (9.9): 7.489 (8.2); 7.448 (0.5); 2.469 (1.8); 2.464 (2.6); 2.459 (2.0); 2.157 (1156.2); 2.120 (5.2); 2.114 (6.3): 2.108 (7.5); 2.102 (5.6); 2.096 (3.3); 1.965 (26.5); 1.959 (71.5); 1.953 (401.8); 1.947 (750.3); 1.941 (1019.6); 1.935 (723.9); 1.928 (383.2); 1.781 (2.7); 1.775 (4.6); 1.769 (6.2); 1.763 (4.5); 1.757 (2.6); 1.634 (0.6); 1.597 (4.4); 1.583 (11.2); 1.576 (11.2); 1.563 (6.0); 1.523 (1.0); 1.437 (16.0); 1.401 (1.1); 1.361 (6.0); 1.347 (11.3); 1.341 (12.0); 1.326 (4.9); 1.270 (8.5); 0.882 (2.0); 0.857 (2.2); 0.000 (34.6) Example l-T3—188: 1H-NMR (400.0 MHz. CD3CN); 8:: 8.340 (9.9); 8.272 (16.0): 8.192 (07.3);77761 (9. 7_;) 7 755 (123);7 .742 (0. 4). 7. 737 (0. 3); 7.727 (6. 7): 7. 721 (5.0). 7.706 (7.8); 7. 700 V170 37647 - 248 — (5 5). 7 559 (4.5). 7.524 (11.5); 7.503 (9.3). 5.447 (0.8); 2.575 (0.8); 2.572 (0.8); 2.250 (0.4); 2 139 (89 4); 2.120 (0.7); 2.114 (0.7); 2 108 (0.9); 2.102 (0.8); 2.095 (0.3); 1.955 (3.2); 1.959 (8.4); 1 953 (52.4); 1.947 ; 1940(1322); 1.934 (91 5); 1.928 (47.5); 1781 (0.3); 1.775 (0.5); 1.769 (0 8); 1.753 (0.5); 1.604 (5.0); 1.590 (12.7); 1.583 (12.8); 1.589 (5.7); 1.529 (0.9); 1.408 (0.8); 1.355 (5 8); 1 352 (12.5). 1.345 (13.2); 1.331 (5.3); 1.309 (0.5); 1.293 (0.9); 1.285 (1.5); 1.259 (7.2); 0.898 (0.3); 0.881 (0.9); 0.854 (0.4); 0.000 (3.9) Example l-T3-189: 1H—NMR (400.0 MHz. CD3CN): 8: 8.726 (0.3); 8.720 (0.4); 8.701 (10.1); 8.694 (10.3); 8.265 (0. 8); 8.253 (16. 0); 8.246 (15. 9); 8.062 (0. 6); 8051 (11.3); 8.045 (11.1); 7.978 (7. 4); 7766 (6. 5); 7.051 (2.2); 5. 449 (0. 6); 4.068 (0.4); 4.050 (0.4); 3.024 (0.4); 2.888 (0.6); 2.878 (1.7); 2.869 (2.5); 2.860 (3. 8); 2. 851 (3.8); 2. 842 (2. 5); 2. 833 (1. 8); 2. 823 (0. 6); 2. 729 (0.6); 2.473 (0. 5); 2. 468 (0. 9); 2.464 (1. 2); 2.459 (0 9); 2. 454 (0. 5); 2.166 (234. 9); 2121 (0.;8) 2.114 (1 .;2) 2.108 (1. 5); 2.102 (1. 1); 2.096 (0. 6); 2.087 (0. 5); 2.035 (0.;4) 2.017 (0. 7); 1.998 (0. 6); 1.972 (2.;6) 1965 (5.7); 1959 (13.8); 1.953 (85.4); 1947 (157. 6); 1941 (2155) 1935 (150.1); 1928 (78.1); 1782 (0.5); 1775 (0.9); 1769 (13); 1763 (0. 9); 1757 (05); 1.437 (3.4); 1.308 (0. 3); 1.268 (8. 7); 1222 (0.;6) 1.204 (1. 0); 1.186 (0 5); 0.898 (04); 0.881 (1. 1); 0.864 (0. 5); 0.810 (2. 1); 0.797 (6.2) .792 (8.4); 0.779 (8.6); 0.774 (6.4); 0.762 (2.8); 0.740 (0.4); 0.722 (0.4); 0.662 (0.3); 0.652 (0.4); 0.622 (2.8); 0.610 (7.3); 0.604 (7. 7) 0.600 (6.9); 0.595 (6.8); 0.582 (2.1); 0.543 (0.4); 0.391 (0.3); 0.386 (0.3); 0.008 (1.2); 0.000 (38.3); -0.009 (1.6) Example l-T3-190: 1H-NMR (400.0 MHz. ds-DMSO): 8: 9.487 (7.1); 9.105 (5.1); 9.102 (5.1); 8.887 (9.5); 8.557 (11.6); 8.317 (0.4); 7.826 (4.4); 7.820 (6.3); 7815 (6 9); 7.810 (5. 3); 7.602 (5.1); 7.591 (1.5); 7.580 (4.2); 4.055 (1.3); 4.038 (3.8); 4.020 (3.8); 4.002 (1 .3); 3.560 (1.9); 3.542 (6. 2); 3.523 (6.3); 3.505 (21); 3.328 (157.1) 2.671 (1.6); 2.506 (190.5); 2.502 (243.8); 2.329 (1.7); 1.989 (16.0); 1.617 (2.3); 1.602 (6.1); 1596 (6. 6); 1. 583 (2.7); 1.296 (2.7); 1.28 A6.2); 1.276 (6.6); 1.261 (2.3); 1.193 (4.5); 1.181 (7.3); 1.175 ; 1.163 (14.9); 1.158 (7.2); 1.145 (6.8); 0.000 (25.1) Example 1191; ‘H-NMR (400.0 MHz. 53-01180); : 9.428 (3.3); 8.594 (4.8); 8.359 (4.8): 8.317 (0.5); 7.785 (4.0); 7.779 (2.8); 7.770 (2.1); 7.755 (1 .1); 7.545 (2.7); 7.537 (0.5); 7.530 (0.5); 7.522 (2.3); 7.351 (8.5); 3.331 ); 3.015 (2.0); 2.997 (6.6); 2.979 (8.7); 2.950 (2.1); 2.676 (1.1); 2.571 (1.5); 2.557 (1.2); 2.524 (4.4); 2.511 (85.9); 2.507 (177.3); 2.502 (235.3); 2.498 (176.3); 2.493 (90.0); 2.333 (1 .1); 2.329 (1.5); 2.324 (1.2); 1.811 (1.1); 1.597 (2.7); 1.590 (2.9); 1.577 (1.2); 1.398 (15.1); 1.285 (1.3); 1.271 (2.7); 1.254 (2.9); 1.250 (1.1); 1.195 (7.5); 1.177 (15.0); 1.158 (7.3); 0.145 (1.7); 0.008 (13.5); 0.000 (371.8); —0.008 (15.5); —0.150 (1.7) Example l-T3—192: 1H-NMR (400.0 MHz. de—DMSO): 8: 9.435 (6.5); 8.687 (9.2); 8.408 (9.3); 8.317 (1.5); 7.796 (4.7); 7.787 (4.3); 7.780 (6.0); 7.775 (6.7); 7.770 (5.2); 7.764 (2. 0); 7559 (5.8); .548 (5.4); 7.537 (5.3); 3.330 ); 3.123 (0.7); 3.082 (1.9); 3.063 (6.4); 3.045 (6.6); 3.027 (2.0); 2.838 (0.6); 2.676 (2. 8); 2.671 (4.1); 2.667 (31); 2.525 (10.0); 2520 (15.7); 2511 (220.9); 2. 507 (459.4); 2.502 (612.6); 2. 498 (450. 6); 2.493 (223.7); 2.333 ( 9); 2.329 (4. 0); 2.324 (3. 0); 1614 (2.1); 1.600 (5. 3). 1593 (5.7); 1580 (2.4); 1284 (25); 1271 (53); 1264 (5.7); 1250 (2.1); 1205 (7.5); 1187 (16.0); 1168 (7.5); 0.146 (1.8); 0.008 (13.1); 0000 (4040); 0009 (155) -0.150 (1.8) Example l-T3—19311H-NMR (400.0 MHz. ds—DMSO): 8: 9.458 (0.3); 8.777 (8.3); 8.542 (3.2); 8.531 (3. 0); 8.504 (0. 3); 8.462(8. 6); 8.337(3. 7); 8317 (1 8); 7.962(3 6.); 7.750 0;) 7.745 (3. 2); 7.738 (1.0); 7.726 (12.9); 7.717 (1.1); 7.710 (1.7); 7.692 (1. 1); 7.659 (1.1), 7.653 (0. 9); 7. 569 (1. 2). 7. 548 (1. O); 7.529 3.7;) 7.526 (2.4); 7.510 (2.0); 7.507 (3.2); 7.484 (1.3); 7.465 (0.8); 7.420 (0. 5); 7.402 (0. 6); 7.058 (1.6); 6.924 (3. 7); 6. 789 (1. 9); 4.055 1 .2;) 4.037 (3.6); .020 (3.6); 4.002 (1.2); 3.328 ; 3.305 (0.8); 2.858 (0.9); 2.849 (1.2); 2.840 (1.9); 2.830 (1.9); 2.821 (1. 3); 2.812 AAAA0. 9); 2. 801 (0.4); 2.676 (1.1); 2.671 (1.6); 2.667 (1.2); 2.662 (0.6); 2.524 (3.6); 2.511 (83.9); 2.507 (175.0); 2.502 (233.7); 2.498 (171.2); 2.493 (84.1); 2.338 (0.5); 2.333 (1.1); 2.329 (1.5); 2.324 (1.1); 1.989 (16.0); 1.234 (0.8); 1.193 (4.2); 1.175 (8.4); 1.157 (4.2); 0.729 (1.2); 0.716 (3.5); 0.711 (4.9); 0.699 (4.5); 0.693 (4.0); 0.682 (1.6); 0.568 (0.4); 0.559 (1.8); 0.549 (5.1); 0.543 (4.5); 0.534 (3.7); 0.522 (1.2); 0.146 (0.4); 0.008 (2.5); 0.000 (83.8); -0.009 (3.2); -0.150 (0.4) Example 1-13194; 1HNMR (400.0 MHz. 003011): :8.349 (9.;1) 8.304 (0.4); 8.288 (14.8); 8.241 (0.3); 7.801 (9.7); 7.795 (11.3); 7.718 (5.0); 7.712(55); 7.897 (7.3); 7.892 (59) 7.665 (0.5); 7.847 (07) 7.543 (0.7); 7.535 (0.5); 7.517 (0.5); 7.514 (0.7); 7.584 (1.1); 7.541 (0.5); 7.522 (11.4); 7.501 (9.2); 7.484 (0.5) 7453 (4.1;) 7.422 (0.4); 7.235 (0.4); 7.215 (0.3); 5.837 (0.5); 5.873 (0.4); 5.517 (1.3); 5.575 (0.4); 5.973 (0.3); 5.954 (0.3); 5.895 (1 .;4) 5447 (5.8;) 3817(08) 3.759 (0.4); 3.550 (1.0); 3.545 (0.9); 2.579 (0.4); 2.575 (0.5); 2.259 (0.4); 2.253 (0.5); 2.140 (512.8); 2.120 (72); 2.114 (5.9); 2108 (79) 2102 (55) 2095 (31) 1955 (253) 1959 (535) 1953 (4114) 1947 (7688) 1940 (10551) 1934 (751 .10);1.928 (405.5); 1849 (12); 1799 (07); 1781 (28) 1775 (48) 1759 (57) 1753 (47) 1755 (27) 1728 (05) 1714(05) 1599 (05) 1.577 (0.4); 1666 (0.;5 1.649 (0.4;) 1.628 (0.;4) 1580 (0.;4) 1.570 (0.4) 1.556 (0.;4) 1.515 (0.6) 1.477 (5.4) 1.466 (14.4) 1.457 (16.0 l‘ 1.447 l6.5); 1407 (0.;7 1398 (0.5); 1386 (0.8); 1.366 (0.5); 1.340 (6.0); 1.305 (1.0); 1.285 (8.1); 1.270 (5.0); 1.247 (0.7); 1.230 (0. 5l 1.217 (0.6); 1.199 (0.5; 1. 190 (0. 6); 1.185 (0.7); 1.145 (6.1); 1.135 (15.7); 1.126 (14.8); 1.115 (5.4); 1.076 (0.6); 1.063 (0.4); 0.994 (0.4l 0.976 (0.8); 0958 (0. 5; 0.951vvvv (0.4); 0.930 (0.4); 0.923 (0.4); 0.882 (1.1); 0.856 (0.9); 0.842 (0.7); 0.783 (0.4); 0.771 (0.4); 0.764 (0.5) (0 4.) 0597 (0.3); 0.564 (0.4); 0.008 (1 .0); 0.000 (32.8) Example l-T3-19511H-NMR (400.0 MHz. O): 8: 9.457 (8.1); 8.920 (11.3); 8.511 (11.3); 8.325 (5.6); 8.3'19 (6.1); 8.030 (5.3); 7.802 (8.5); 7.797 (7.4); 7.789 (5.4); 7.784 (3.0); 7.591 (6.0); 7.582 (1.3); 7.569 (5.0); 4.037 (0.6); 4.019 (0.6); 3.329 (278.3); 3.090 (0.5); 3.071 (1.9); 3.053 (2.4); 3.037 (2.5): 3.019 (2.1); 3.000 (0.7); 2.675 (3.1); 2.671 (4.3); 2.667 (3.5); 2.597 (0.4); 2.506 (494.1); 2.502 (653.4); 2.498 (511.0); 2.470 (6.8); 2.452 (3.7); 2.434 (2.4): 2.416 (1.0); 2.333 (3.0); 2.329 (4.1); 2.325 (3.3); 1.989 (2.4); 1.621 (2.6); 1.607 (6.7); 1.600 (7.6); 1.587 (3.1); 1.397 (1.3); 1.335 (0.4); 1.327 (0.3); 1.297 (0.8); 1.286(2); 1. 273 (7.0); 1.266 (7. 6); 1. 252 (3. 2); 1.235 (5.1); 1.193 (0.7); 1.175 (1.3); 1.157 (0.7); 1.107 (0.4); 0.982 (7.4); 0.964 ; 0.945 (7. 3); O.854 (0. 5); 0.835 (0.3); 0.000 (20.8) Example I—T3-196: 1H-NMR (601.6 MHz. CDSCN): : 8.223 (0.5); 8.218 (0.5); 8.045 (0.3); 8.041 (0.3); 2.621 (0.7); 2.150 (4.8); 1.948 (1.3); 1.944 (2.2); 1.940 (3.2); 1.936 (2.2); 1.932 (1.1); 1.135 ; 0.000 (0.9) Example l—T3«197: 1H—NMR (601.6 MHz. : 8: 8.765 (7.5); 8.761 (7.5); 8.2493 (9.5); 8.2486 (9.9); 8.230 (8.0); 8.115 (8.0); 8.111 (8.0); 8.038 (4.4); 7.992 (4.5); 7.394 (1.5); 3.844 (16.0); 3.552 (11.2); 3.542 (11.1); 3.312 (0.7); 3.303 (0.7); 2.172 (78.0); 2.155 (28.3); 2.088 (0.6); 2.084 (0.8); 2.080 (0.6); 1.998 (2.0); 1.989 (5.4). 1. 985 (7. 5); 1. 982 (52.9); 1.977 (98 7); 1. 973 (145.4); 1. 969 (98.4) 1. 965 ; 1956 (0.7); 1. 863 (0. 5); 1 859 (0.8); 1.854 (0.6); 1312(27); 1303 (81); 1299 (80); 1291 (3.5); 1266 (04) 1192 (04) 1166 (35); 1158 (79); 1154 (79); 1146 (2.6) Example I 8: 1H—NMR (400. 0 MHz. ds—DMSO) ‘NO 2015/067647 - 249 — 7778 13 2) 7.765 12.2); 7.759 (1 3);779 (28) 7.525714;) 4.049104); 3.497 (0.3); 3.479107). 3.461 (07); 3.413 (10); 3.395115); 3.377116) 3.329 ; 3.267 (1 ) 2.676140) 2.671 15 5); 2.667 14.1); 2.524 ; 2.507 (629.0); 2.502 (626.7); 2.498 (606.0); 2333136) 2329(5.2);2324139),1 614113); 1. 6900(3.4) 1.593137); 1.560115); 1.269115); 1.276133); 3.6); 1.255113). 04) 1150(04;.);1.126(07)11 06163;) 069 (16.0;)1.071(7.0);0.00610.5);0.000(169);-0.006(0.7) Example 173199; 11+NMR (400.) MHz. d6DMSO): 0: 666 (00328) 885 (00664) 656 10.0471),6.51 (0.;..;.0250)616(00290)617 (0..0296);609 (0.0245);..347(00401);.345 (0.0407);.331 (0.7767)254 (0.;3233)2.50 (0.;.3250)250 (04;.400)250 (0.;3578)125 (0.;.0306)125 (0.;.0369)115 (0.;0210)1.14 (0.0347);.113 (0.0321);0.0011.0000) Example l-T3-200: 1H-NMR (4000 MHz. CD3CN): 6:8.745 (6.9); 8.739 (6.9); 6.566116); 6.560 (1.6); 6.264 (13.9); 6.256 (14.3); 6.244 (0.7;) 6.115 (9.6); 6.109 (9.4;) 6.056 (16.); 8.050 (1.;7) 7.996 (0.4); 7.963 (7.2); 7.960 (7.2); 7.767 (6.3); 7.690 (2.3); 7.666106); 7.567 (0.3;) 5.34461. 1); 3.724 (0.6); 3.071 (05;) 2.662 (0.5;) 2.60.2617); 2603 (0.5); 2.468 (0.4); 2.463 (0.5); 2.456 (0.4); 2.152 (189.2); 2.120 (14) 211411.;6) 2106 (21) 2102 (1.5;) 2.096 (0.8;) 1.8965( .;9) 1959 (23.8); 1.953 (126.4); 1.947 (227.5); 1.941 (305.0); 1.935 (2126),)926 (11.;6) 1868(03), 1.781 (0.6); 1775 (1.;4) 1.7169( 9), .); 1757107) 1..;615(39) 1600 (10.0); 1.593 (10.8); 1.580 (67) 157112 .;5) 1557113); 1540107) 1410 (0.;6) 1.386(0 .;4) 137015.); 1356(100) 13501104) 1.335153); 1.325123); 1.31011. 1); 1.02971 .;5) 1.265107); 1.270124) 1202 (0.6); 1.134 (160); 0.662 (0.4); 0.006 (0. 5); 0.000 (1 5. 0); 0.006 (0.3) Example 1201: ‘H-NMR (400.0 MHz. 660117160); 6: 9.467 (2.2); 6.775 (3.1); 8.578 (1.5); 8.573 (1.5); 6.490 (3.1); 6.177 (1.4); 7.600 (0.6); 7.795 (1.2); 7.787(1. 6); 2.4); 777611.9); 7576 (1.;7) 7555 (15); 3498 (06) 34.79119), 3.461 (1 9); 3443 (06) 3330 (1985) 2676107) 2.671(1.0);2.667 (0.7); 2524125) 2507 (1072) 2502 (141.6); 249611061) 2333107) 2329109) 2325107) 1989(04) 1.614(07); 1600 (18) 1593 (19); 1.580 (0.;8) 1396 (160) 1287 (06) 1274 (18) 1267120) 1253107) 1.235103); 21); 1..;108147) 1.2089(.1;) 0.146 (0.9); 0.006 (7.;4) 0.000(188.;9) —0008 (67) 01.50109) e 1—73—202; ‘H-NMR (400.0 MHz. O): 6: 9.428 (4.6); 6.626 (0.4); 8.603 (6.6); 6.357 (6.9); 6.316 (0.6); 7.790 (1.3); 7.765 (2.6); 7.777 (4.1); 7.772 (5.1); 7.766 (4.0); 7.562 (3.3); 7548 (39) 7.537 10.6); 7.5.25132); 7.426132) 334313905) 2991 (1. 5). 2.97314 6); 2.955 (5.;1) 2.937 (1.6); 2.676 (10.); 2.672(13); 0); 250711632) 060) 2.49911522), 2.334110); 2.33011 3), 2325109), 2166110); 2..;100(160) 2075105) 1613 (1.;6) 1596 (41) 1592 (45) 1579120) 1264120) 1270143) 1263145) 1249116) 1232104) 7) 1192155) 1173 1114;)1.1.;55152)0..;146105)00;06149)00.;0011171) 0..;006149) 0.150106) Example 03: 1H—NMR (400.0 MHz. ds—DMSO): 8: 8.601 (0.6); 8.581 (6.8); 8.520 (2.4); 8.509 (2.4); 8.343 (7.1); 8.137 (0. 8); 7.732 (1.5); 7.726 (2.4); 7.707 (9.8); 7.561 (3.2); 7.499 (2.9); .477 (2.5); 7.427 (3.2); 3.329 (31 .4;) 2.989 (1.5); 2.971 (5.0); 2.952 (5.1;) 2. 940 (07); 2.934 (1 .;6) 2.922 (0. 4); 2.854 (0. 6); 2.844 (0. 9); 2.836 (1 .;4) 2.826 (1 .;4) 2.818 (1 .;O) 2.808 (0.7); 2.676 (0. 5); 2.671 (0.7); 2. 667 (0. 5); 2. 524 (1. 7)', 2. 511 (394); 2.507 (80. 4), 2.502 (106. 1); 2498 (782); 2.333 (0.;5) 2.329 (0.7); 2.324 (0.;5) 2.187 (1.2); 2.116(0.;8) 2.101 ; 2.075(1.) 1909 (0.5); 1230 (0.4); 1212 (0.9); 1.190 (5.7); 1.172 (11.9); 1.154 (5.4); 0.726 (0.9); 0.713 (2.6); 0.708(3 .;6) 0.696 (3.5); 0.690 (3.0); 0.679 (1. 3); 0.560 (1.2); 0.550 (3.7); 0.544 (3.5); 0.534 (3.0); 0.522 (0.9); 0.008 (2.2); 0.000 ; -0.008 (2.8) Example l—T3-204: 1H-NMR (400.0 MHz. O): 6: 8.968 (6.3); 8.871 (0.8); 8.864 (4.0); 8.858 (3.7); 8.617 (5.8); 8.558 (2.8); 8.554 (2.9); 8.469 (3.0); 8.464 (2.8); 8.379 (3.8); 8.373 (3.6); 8.318 (1.3); 8.261 (0.5); 8.255 (0.6); 4.155 (14;.) 3.332 (210.2); 3.309 (0.8); 3.036 (16.0); 3.014 (1 O); 2.886 (0. 9); 2.809 (0. 3); 2.798 (0.7); 2.791 (0.8); 2.782 (13;.) 2.772 (1.0); 2.762 (3.0); 2.727 (0.4); 2.676 (0.8); 2.672 (1.1); 2.667 (0.9); 2.541 (0.4); 2.525 (2.7); 2.511 (61.5); 2507 (127.7); 2.503 (170.1); 2.498 (126.6); 2.494 (64.4); 2.334 (0. 8); 2.329 (1.1); 2.325 (0.9); 2075 (2. 2); 1.169 (0. 5), 0.836 (0.3); 0.817 (0.4); 0775 (0. 4); 0.608 (0.4); 0.587 (2.1); 0.579 (2.6); 0.570 (1.1); 0.562 (0.6), 0.544 (10;.) 0.532 (21); 0.515 (2.1); 0.496 (0.5); 0.146 (0.4); 0.008 (2.9); 0.000 (95.4); -0.008 (4.6); -0.150 (0.4) Example I-T3-205: 1H-NMR (400.0 MHz. ds-DMSO): 8: 8.991 (0.5); 8.972 ; 8.876 (0.4); 8.861 (9.9); 8.855 (10.1); 8.716 (4.8); 8706 (5.3); 8. 672 (04.) 8.661 (0.4); 8.642 (0.8); 8.631 (14.8); 8.562 (7.0); 8.557 (7.2); 8.471 (7.3); 8.467 (6.8); 8.318 (8.7); 8. 264 (0. 7); 8. 258 (0. 8); 8.247 ( .6); 8. 240 (9.4); 7.948 (0.4); 7.942 (0.4); 7.795 (0.4); 4.156 (4.3); 3.329 (163.2); 3.306 (4.7); 2.887 (0.6); 2.877 (1 .4;) 2. 867 (2.0); 2.859 (3.0;) 2.849 (3.2), 2.840 (2 2); 2830 (1.7); 2.821 (0.8); 2.676 (1.6); 2.671 (2.1); 2.667 (1.6); 2.525 (5.4); 2.507 (239.7); 2.502 (316.6); 2.498 (235.7); 2.333 (1 4;.) 2329 (2.0); 2.325 (1.5); 2.076 (16.0); 0.760 (1.9); 0.747 (5.6); 0.743 (7.6); 0.730 (7.4); 0.725 (6.3); 0.713 (2.8); 0.570 (2.3) 0.559 (7. 1); 0.553 (7.0); 0.550 (6.7); 0.544 (6.4); 0.532 (2.3); 0.495 (0.4); 0.146 (0.8); 0.008 (5.8); 0.000 (177.1); -0.008 (8.0); -0.150 (0.8) Example l-T3-206: 1H-NMR (400.0 MHz. de-DMSO): 6: 9.449 (4.9); 6.659 16.6); 8.459 (6.7) . 2); 6036 (30) 7936 (3.0); 7.603 (3.4); 7.799 (4.7); 7.793 (4.8); 7.787 (3.7); 7.761 (1.6); 7.581 14.2); 7.570109); 7.556 (3.6); 3.733 (0.3); 369010.4); 3329 (896.7); 3.262 (0.7); 2.981 (1.3); 2.963 (1.5); 2.947 (1.5); 2.929 (1.4): 2910105); 2676(76)2671 ; 2667177); 2.525 (264;) 2511 (569.6); 2.507 (1166 5) 2502115552) 2496111461) 2493 (5786) 2369 (16); 2370(1.8); 2354116); 2333 (80) 2329 (104) 2324 (77) 2296 (160) 1909 (06) 1.621(16.); 1607 (40) 1.600 (4.;3) 1567120) 1262 (21) 12.69139) 1..;262(42) 1246116) 1147106) 0945 (48) 09271105) 0906146) 0146136) 0.006 (30.4); 0.000 (660.4); -0.008 (42.5); 0.150 (37) Example I—T3-207: 1H—NMR (400.0 MHz. ds-DMSO): 8: 9.624 (6.5); 9.586 (0.7); 8.984 (9.3); 8.916 (5.7); 8.910 (5.5); 8.728 (0.7); 8.636 (9.3); 8.571 (1.5); 8.560 (4.6); 8.473 (4.6); 8.469 (4.3); 8.330 (6.1); 8.324 (6.0); 7.943 (0.4); 7.798 (0.4); 7.793 (0.4); 4.156 (3.5); 3.332 (174.7); 3.051 (0.6); 2.875 (0.6); 2.672 (1.1); 2.667 (0.9); 2.507 (117.6); 2.503 (153.3); 2.499 ); 2.330 (10); 2.325 (0. 7); 2.076 (16. 0); 1.648 (2. 1); 1.634 (5.4); 1627 (6. 2); 1.614 (2.5); 1.304 (2.4); 1291 (5.2); 1284 (37); 1269 (2.1); 1262 (0.8); 1254 (07); 1240 (03); 0.146 (04); 0008 (28) 0000 (781); -0.150 (0.4) Example 1 73-208: 1H—NMR (400.0 MHz. : 6:6.696130); 6690131,) 6249142); 6240146), 8..003(32), 7997 (31) 7.962123); 7.976(2.3);7946105);7.940(0.5);7.766 (2.1): 3.068(16.0); 2.600 12.7); 27.63106) 2776 (06) 2767 (1 1); 2756 (07); 2746 (0.6); 2.465 (04) 2170 (943) 2.115 (0.5); 2.109 (0.6); 2.102104); 1.965127); 71); 1.9541391); 1..;9471710) 1.941 (94 9); 1.935 (64.6) 1929 (331) 1776104); 1770105); 1.763 (0.4); 0.655 (0.3); 0.769 (0.4); 0.579 (1.4); 0.535 11.7); 0.525 (1.)); 0.516 (1.6); 0.000 (0.5) Example 1—73-209; 1H-NMR (400.0 MHz. d6-DMSO): 6: 9.461146); 6.713 16.6); 6.446 (6.6); 6.317 (1.4); 6.261 (3.0); 31); 7.800 11.3); 7.794 (2.6); 7.767 (4.1); 7.762 (5.1);7.77614.1)_; V40 2015/067647 - 250 — 7.569 (3.8); 7.557 (0 8); 7 546 (3.2); 3.393 (0.4); 3.331 (347.0). 2.676 (2.0); 2 672 (2 7). 2.667 (21); 2.524 (7 4); 2.507 (323.5); 2.503 (427.2); 2.498 (324.8); 2.426 (0.4); 2.334 (1.9); 2.329 (2.7). 2.325 (2.1); 2.197 (0.8); 2.160 (16.0); 1.614 (1.5); 1.600 (4.0); 1.593 (4.4): 1.580 (1.8); 1.284 (1.8). 1.270 (4 0); 1.264 (4.4). 1.249 (1.5). 1 147 (0 6); 1.079 (4.6); 1.06l (101); 1.042 (4 5); 0.146 (0.9); 0.008 (6.6); 0.000 (197.0); 0.150 (1.0) Example 173—210; ‘H-NMR (400.0 MHz. (11-00160); 8: 8.835 (0.4); 8.692 (6.8); 8.552 (2.5); 8.540 (2.5); 8.513 (0.5); 8.435 (7.0); 8.318 (0.5); 8.278 (3.0); 8.094 (3.0); 7.873 (0.4); 7.742 (1.5); 7.736 (2.5); 7.718 (10.2); 7.520 (3.0); 7.502 (1.5); 7.498 (2.5); 3.357 (1.0); 3.329 (76.1); 3.304 (1.0); 2.857 (0.6); 2.847 (0.9); 2.839 (1.4); 2.829 (1.4); 2.820 (0.9); 2.811 (0.7); 2.676 (0.8); 2.671 (1.1); 2.667 (0.9); 2.524 (3.0); 2.511 (66.6); 2.507 (135.2); 2.502 (178.3); 2.498 ); 2.493 (64.6); 2.333 (0.9); 2.329 (1 .2); 2.324 (0.9); 2.193 (1.1); 2.159 (16.0); 2.075 (0.6); 1.153 (0.3); 1.135 (0.7); 1.078 (4.8); 1.060 (10.5); 1.041 (4.6); 0.727 (0.9); 0.714 (2.6); 0.709 (3.6); 0.697 (3.5); 0.691 (3.0); 0.680 (1.3); 0.559 (1.2); 0.548 (3.6); 0.542 (3.3); 0.539 (3.1); 0.533 (3.0); 0.521 (0.9); 0.146 (0.4); 0.008 (3.0); 0.000 (92.3); -0.008 (3.7); 0.150 (0.4) Examp1e |-T3-211: 1H-NMR (400.0 MHz. ds-DMSO): 6: 8.641 (0.5); 8.541 (0.8); 8.530 (3.2); 8.524 (3.1); 8.504 (5.0); 8.495 (0.7); 8.385 (0.5); 8.318 (1.5); 8.288 (5.2); 8.280 (0.8); 7.971 (3.1); 7.965 (3.0); 7.943 (0.5); 7.803 (0.8); 7.532 (2.9); 7.375 (2.7); 7.322 (0.3); 7.209 (0.3); 4.421 (0.8); 4.404 (2.1); 4.386 (2.3); 4.369 (1.0); 4.240 (1.1); 4.224 (3.6); 4.206 (3.6); 4.189 (1.2); 4.179 (0.5); 4.162 (0.4); 3.741 (0.4); 3.727 (0.4); 3.328 (176.8); 3.027 (0.8); 2.985 (16.0); 2.886 (0.8); 2.775 (0.5); 2.762 (1.0); 2.748 (1.4); 2.734 (1.2); 2.717 (2.0); 2.676 (2.7); 2.671 (3.8); 2.667 (2.8); 2.524 (10.0); 2.510 (212.4); 2.507 (426.0); 2.502 (559.5); 2.498 (412.6); 2.456 (0.7); 2.333 (2.6); 2.329 (3.5); 2.324 (2.7); 2.075 (1.5); 1.361 (0.8); 1.344 (1.7); 1.329 (5.1); 1.312 (10.0); 1.294 (5.0); 1.282 (0.6); 1.229 (0.6); 1.213 (4.5); 1.196 (8.4); 1.178 (4.2); 1.160 (0.4); 1.147 (0.4); 0.788 (0.3); 0.779 (0.4); 0.704 (0.4); 0.469 (4.1); 0.454 (2.9); 0.146 (1 .0); 0.008 (7.5); 0.000 (219.5); -0.008 (9.3); -0.150 (1.0) Example l-T3-212: 1H-NMR (400.0 MHz. ds—DMSO): 8: 9.450 (2.0); 8.714 (2.7); 8.433 (2.7); 8.220 (1.3); 8.083 (1 .3); 7.802 (0.5); 7.796 (1.2); 7.790 (1.7); 7.785 (1.8); 7.780 (1 .4); 7.774 (0.6); 7.567 (1.5); 7.556 (0.4); 7.545 (1.3); 3.329 ; 2.675 (0.5); 2.871 (0.7); 2.667 (0.5); 2.506 ; 2.502 (103.1); 2.498 (77.2); 2.329 (0.7); 1.615 (0.6); 1.601 (1.6); 1.594 (1.7); 1.581 (0.7); 1.398 ; 1.287 (0.7); 1.274 (1.6); 1.267 (1.7); 1.253 (0.6); 0.008 (1.3); 0.000 (41.2); —0.008 (1.8) Example I-T3-213: 1H-NMR (400.0 MHz. d8 — Ix.) U1 4; I Biolopical Examples ephalus sanguineus - in vitro contact tests with adult brown dog ticks For the coating of the test tubes, 9 mg of active ingredient are first dissolved in 1 m1 of acetone 250 ul of the solution are distributed p.a. and then diluted to the desired concentration with acetone p.a. homogeneously on the inner walls and base of a 25 m1 test tube by g and rocking on an orbital shaker (rocking rotation at 30 rpm for 2 h). With 900 ppm active ient solution and internal surface 44.7 cmz, given homogeneous distribution, an area-based dose of 5 ug/cm2 is achieved.
After the solvent has evaporated off, the tubes are ted with 5-10 adult dog ticks (Rhipicephalus sanguineus), sealed with a perforated c lid and incubated in a horizontal position in the dark at room temperature and ambient humidity. After 48 h, efficacy is determined. To this end, the ticks are knocked to the floor of the tube and ted on a hotplate at 45—50°C for not more than 5 min. Ticks which remain motionless on the floor or move in such an uncoordinated manner that they are unable to rately avoid the heat by climbing upwards are considered to be dead or moribund.
A substance shows good efficacy against Rhipicephalus sanguineus if at least 80% efficacy was achieved in this test at an application rate of 5 . An efficacy of 100% means that all the ticks were dead or moribund. 0% efficacy means that none of the ticks had been harmed.
In this test, for example, the following nds from the preparation examples show an y of 100% at an application rate of 5 ug/cmz: I-T3-1, I-T3-3, I-T3-20, I—T3-21, I—T3-23, I-T3-24, I-T3-42, 4, I—T3—46, I—T3—47, 2, I—T3-53, I—T3-54, l-T3-55, I—T3—56, I-T3-61, I-T3—63, I—T3- 71, I—T3-72, I-T3-81, I—T3—90, 1, I-T3-96, 7, I—T3-98, I-T3-104, I—T3-106, I-T3-109, I-T3- 110, I-T3—112, I-T3-117, l-T3-119, I-T3—148, I—T3-155, I-T3—160, I—T3—161, I-T3—162, I-T3-163, I—T3- 165, I—T3-175, I—T3-176, I—T3-189, I—T3-196, I—T4-1, , I—T4-3, I—T4-4, I—T22-2, I—T22-1, I—T22-4, I—T22-5, I-T22-6, I—T22-7 In this test, for example, the following compounds from the preparation examples Show an efficacy of 80% at an application rate of 5 ug/cmz: I—T3—38, I—T3-43, 0, I—T3-88, I-T3-92, I—T3- In this test, for example, the following compounds from the preparation examples show an efficacy of 100% at an application rate of 1 ug/cmzz 08, I-T3—1 14, I—T3-141 In this test, for example, the following compounds from the preparation examples show an efficacy of 80% at an application rate of 1 ug/cmz: I—T3-94, l-T3—123 In this test, for example, the following compounds from the preparation examples show an efficacy of 100% at an application rate of 0.2 ug/cmz: I—T3-105 "’0 2015/067647 — Ix) U1 LJ‘I I In this test, for example, the following compounds from the preparation examples show an efficacy of 80% at an application rate of 0.2 ug/cmz: l-T3-64 Ctenocephalides felis — in vitro contact tests with adult cat fleas For the coating of the test tubes, 9 mg of active ingredient are first dissolved in 1 m1 of acetone distributed p.a. and then diluted to the desired concentration with acetone p.a. 250 ul of the solution are homogeneously on the inner walls and base of a 25 ml test tube by g and rocking on an orbital shaker (rocking rotation at 30 rpm for 2 h). With 900 ppm active ingredient on and internal surface area 44.7 cmz, given homogeneous distribution, an area-based dose of 5 pig/cm2 is achieved.
After the t has ated off, the tubes are ted with 5-10 adult cat fleas (Ctenocephalides felis), sealed with a ated plastic lid and incubated in a horizontal on at room temperature and ambient ty. After 48 h, efficacy is determined. To this end, the test tubes are stood upright and the fleas are knocked to the base of the tube. Fleas which remain motionless at the base or move in an uncoordinated manner are considered to be dead or moribund.
A substance shows good efficacy against Ctenocephalides felis if at least 80% efficacy was achieved in this test at an application rate of 5 ug/cmz. 100% efficacy means that all the fleas were dead or moribund. 0% efficacy means that no fleas were harmed.
In this test, for e, the following compounds from the preparation examples show an efficacy of 100% at an application rate of 5 tLg/cm2 (= 500 g/ha): I—T3-1, I-T3—3, I—T3-7, I—T3-9, I-T3-l7, I-T3-20, I-T3-21, I-T3—23, I-T3-24, I-T3-25, I-T3-27, 8, I—T3-29, I-T3-30, I-T3-31, I-T3-42, I-T3- 43, I-T3-44, I—T3-46, I-T3-54, I—T3-55, I—T3—56, 7, I—T3—6l, l-T3—63, I-T3-64, I—T3-7l, I-T3—72, I- T3-80, I-T3-81, I—T3-84, I—T3—85, I—T3-86, 7, I—T3-88, 1, I-T3-92, I—T3-93, I—T3-94, I-T3- 95, I-T3-96, I—T3-97, I~T3-98, I-T3-99, I—T3-100, I—T3-101, I—T3-102, I-T3-103, I-T3-106, I-T3-107, I- T3-108, I—T3-109, l-T3—110, I-T3-111, I—T3—112, I-T3—ll3, I-T3-114, I—T3—115, I-T3-ll6, I-T3-ll7, I- T3-118, I-T3-ll9, I—T3-120, I-T3-123, I-T3-124, I-T3-125, I—T3-127, I—T3—128, I—T3-129, I—T3-130, I- T3-131, l—T3-l32, 33, I-T3-l36, I—T3-137, I-T3-l38, I-T3-l43, I-T3-l45, 47, I-T3-148, I- T3-155, I-T3-160, I—T3-162, I-T3-163, I-T3—l65, 75, I—T3-176, I—T3—189, I—T3-196, I-T3-199, I- T4-2, I—T4—3, I-T4-4, I—T22-1, I-T22-2, I-T22-3, I-T22-5, I-T22-7, I—T23—l, I-T23-2, I—T46—2 Amblyomma hebaraeum test Solvent: dimethyl sulphoxide id="p-678" id="p-678" id="p-678" id="p-678" id="p-678" id="p-678"
[678] To produce an appropriate active ient formulation, 10 mg of active ient are mixed with 0.5 ml of dimethyl sulphoxide, and the concentrate is diluted with water to the desired concentration.
‘ - IO U] o" I Tick nymphs (Amblyomma hebmeum) are placed into perforated c beakers and immersed in the desired concentration for one minute. The ticks are transferred on filter paper into a Petri dish and stored in a climate-controlled cabinet.
After 42 days, the kill in % is determined. 100% means that all of the ticks have been killed; 0% means that none of the ticks have been .
In this test, for example, the following compounds from the preparation examples show an efficacy of 100% at an application rate of 100 ppm: I-T3-1, I-T3-3, I-T3-20, I-T3-21, I-T3-24, I—T3-28, 2, I-T3-43, I-T3-44, I-T3-54, I-T3-55, I—T3-56, I-T3-57, I-T3-63, I—T3-64, I-T3-71, I-T3-72, I-T3- 81, I-T3-86, I-T3—91, I—T3-92, I-T3-95, I-T3-96, I-T3—97, I—T3-98, 00, I-T3—104, I—T3-106, I—T3- 107, 08, I—T3-109, I—T3—110, I—T3-112, I—T3—114, I-T3-116, I-T3-117, I—T3—119, I—T3-124, I—T3- 125, I—T3-131, I—T3-148, I—T3—155, I-T3-162, I—T3-163, I-T22—1, I—T22-2, 1, I-T4-3, I-T4—4 In this test, for example, the following compounds from the preparation examples show an efficacy of 95% at an application rate of 100 ppm: I—T3-101 In this test, for example, the following compounds from the preparation examples show an efficacy of 90% at an application rate of 100 ppm: I-T3—102, I—T3-103 In this test, for example, the following compounds from the preparation es show an efficacy of 85% at an application rate of 100 ppm: I—T3-105 In this test, for e, the following compounds from the preparation es show an y of 80% at an application rate of 100 ppm: I-T3—53, I-T3—61, I—T3-111, I-T3—123 Boophilus microplus — injection test Solvent: dimethyl sulphoxide To e an appropriate active ingredient formulation, 10 mg of active ingredient are mixed with 0.5 ml of solvent and the concentrate is diluted with solvent to the desired concentration. 1 ul of the active ingredient solution is injected into the abdomen of 5 engorged adult female cattle ticks (Boophilus microplus). The animals are transferred into dishes and kept in a climate— controlled room.
Efficacy is assessed after 7 days by laying of e eggs. Eggs which are not visibly fertile are stored in a climate-controlled cabinet until the larvae hatch after about 42 days. An efficacy of 100% means that none of the ticks has laid any fertile eggs; 0% means that all the eggs are e. id="p-690" id="p-690" id="p-690" id="p-690" id="p-690" id="p-690"
[690] In this test, for example, the ing compounds from the preparation examples show an efficacy of 100% at an application rate of 20 ug/animal: I—T2-l, I—T2—2, I—T3—1, I-T3-2, I-T3-3, I-T3—4, I— ' — 257 - T3—5, I-T3—6, I-T3—7, I—T3-8, I—T3-9, I—T3-10, I—T3—11, I—T3—12, l—T3—13, l-T3-15, I—T3—l7, I-T3-18, I- T3—l9, I—T3-20, 1, I-T3-23, I-T3-24, I—T3—25, I-T3-26, I—T3—27, I-T3—28, I-T3-29, I—T3—30, I—T3- 31, I-T3-32, I-T3—33, I-T3—34, I-T3-35, I-T3-36, I-T3-37, I-T3-38, I-T3-39, I—T3—40, l, I—T3—42, I- T3-43, I—T3-44, I—T3-45, I-T3-46, I-T3-47, I-T3—48, I-T3-49, 0, I—T3—51, I-T3-52, I—T3-53, I-T3- 54, I-T3-55, I—T3—56, I-T3-57, I—T3-58, I-T3-59, I-T3-60, I-T3-61, I-T3-62, I-T3-63, I-T3—64, I—T3-65, I- T3—66, I—T3-67, I-T3—68, I-T3-69, I—T3-70, 1, 2, I-T3-73, I-T3-74, I-T3-76, I-T3-77, I-T3- 78, I—T3-79, I-T3-80, I-T3-81, I-T3—82, 3, 4, I—T3-85, I-T3—86, I-T3—87, I-T3—88, I-T3-89, I- T3-90, I—T3—91, I—T3-92, I—T3-93, I—T3-94, I-T3-95, I—T3-96, I—T3-97, I-T3-98, I-T3-99, I—T3-100, I-T3— 101, I-T3-102, I—T3-103, I—T3-104, I-T3-105, I—T3-106, I-T3-107, I—T3-108, I-T3-109, I—T3-110, I—T3- 111, I-T3-112, I—T3-113, I—T3-114, I-T3-115, I-T3-116, I-T3-117, I-T3-118, I—T3-119, I—T3-120, I-T3— 123, I-T3-124, I—T3-125, I-T3-126, I-T3—127, I—T3-128, I-T3-129, I—T3-130, I-T3-131, I—T3-132, I-T3— 133, I—T3-136, 37, I—T3-145, I-T3—139, I—T3-l40, I-T3-l4l, I-T3-142, I—T3-143, 44, I-T3— 146, I—T3-148, I—T3—149, I-T3-150, I—T3-151, 55, I—T3-160, I—T3-161, I-T3—l62, I—T3-163, I 165, I—T3-168, I-T3—175, I-T3—l76, 9, I—T4-1, I—T4—2, I—T4-3, I—T4-4, I—T22-1, I-T22—2, I—T22—3, I- T22-4, I-T22-5, I-T22—6, I-T22—7, I-T23-l, 2, I-T46-2 In this test, for example, the following compounds from the preparation es show an efficacy of 90% at an application rate of 20 ug/animal: I-T3 -75 In this test, for example, the ing compounds from the preparation es show an y of 80% at an application rate of 20 [Lg/animal: I-T3—121 Boophilus microplus - dip test Test animals: cattle ticks (Boophilus microplus) Parkhurst strain, SP—resistant Solvent: dimethyl sulphoxide 10 mg of active ingredient are dissolved in 0.5 ml of dimethyl sulphoxide. For the purpose of producing a suitable formulation, the active ingredient solution is diluted with water to the concentration d in each case.
This active ingredient formulation is pipetted into tubes. 8-10 adult engorged female cattle ticks (Boophilus microplus) are transferred into a further tube with holes. The tube is immersed into the active ingredient formulation, and all the ticks are completely wetted. After the liquid has run out, the ticks are erred on filter discs into plastic dishes and stored in a climate-controlled room. id="p-697" id="p-697" id="p-697" id="p-697" id="p-697" id="p-697"
[697] Efficacy is assessed after 7 days by laying of fertile eggs. Eggs which are not visibly fertile are stored in a e—controlled cabinet until the larvae hatch after about 42 days. An efficacy of 100% means that none of the ticks has laid any fertile eggs; 0% means that all the eggs are fertile.
‘ - Ix) U1 (75 | In this test, for e, the following compounds from the preparation examples show an efficacy of 100% at an application rate of 100 ppm: I-T3—l, I-T3—3, l-T3-20, l-T3-21, I—T3-24, l-T3—28, I—T3-39, I-T3-42, 3, I-T3—44, 8, I—T3-53, I—T3-54, l—T3-55, I-T3—56, l—T3—57, I-T3-6l, I—T3- 63, I-T3-64, I—T3-71, I-T3-72, I-T3-81, I-T3-86, I-T3-91, I-T3-92, I-T3-95, I—T3-96, I—T3-97, 8, I- , I-T3—101, I-T3-102, I—T3-103, I-T3-104, I—T3-106, I—T3—107, I—T3-108, I—T3-109, I—T3-110, I— , I-T3-113, I-T3—114, I-T3—115, I—T3—116, I-T3-117, I-T3-118, I-T3-ll9, I-T3—120, I—T3-123, I- , I-T3-125, I-T3—130, 31, I—T3-133, I—T3—l48, I—T3-155, I—T3-160, I-T3-162, I-T3-163, I- T3-165, I—T3-175, I—T3—176, I-T4-3, I—T4-4, I-T22-1, I—T22-2, I—T22-4, I-T22-5, I—T22—6, I—T22-7, I- T23-1 id="p-699" id="p-699" id="p-699" id="p-699" id="p-699" id="p-699"
[699] In this test, for example, the following compounds from the preparation examples show an efficacy of 98% at an application rate of 100 ppm: I—T3—l 11 In this test, for example, the following compounds from the preparation examples show an efficacy of 90% at an application rate of 100 ppm: I-T3-99 In this test, for example, the following compounds from the preparation examples show an efficacy of 80% at an application rate of 100 ppm: 7, I-T3-80 ephalides felis - oral test Solvent: dimethyl sulphoxide For the purpose of producing an appropriate active ingredient formulation, 10 mg of active ingredient are mixed with 0.5 ml of dimethyl sulphoxide. Dilution with ed cattle blood gives the desired concentration.
About 20 unfed adult cat fleas (Ctenocephalidesfelis) are placed into a chamber which is closed at the top and bottom with gauze. A metal cylinder whose bottom end is closed with parafilm is placed onto the chamber. The cylinder contains the active ingredient preparation, which can be d by the fleas through the parafilm membrane. id="p-705" id="p-705" id="p-705" id="p-705" id="p-705" id="p-705"
[705] After 2 days, the kill in % is determined. 100% means that all of the fleas have been killed; 0% means that none of the fleas have been killed.
In this test, for example, the ing compounds from the preparation examples show an efficacy of 100% at an application rate of 100 ppm: I-T3-1, I-T3—2, I—T3-3, I-T3-4, I-T3—5, I-T3—7, I-T3-8, I—T3-9, I- T3—10, I—T3-12, I-T3—18, I—T3-20, I-T3-21, I-T3-23, I—T3—24, 5, I—T3-26, I—T3-27, I-T3-28, I-T3- 29, I—T3-30, I—T3-31, I-T3-32, I—T3—33, 4, I-T3-35, I—T3—3 8, I—T3—39, I-T3-40, I—T3—42, I-T3—43, I- T3-44, 6, I—T3—47, I-T3-48, I—T3-49, I—T3-50, I—T3-51, I-T3-52, I—T3-53, I-T3—54, I—T3-55, I-T3- 56, I-T3-57, I-T3-58, I-T3-59, I—T3-61, 2, I-T3—63, 4, I—T3-65, I-T3-66, I—T3-67, I—T3-68, I— T3-69, I—T3—7l, I-T3—72, I—T3-73, I—T3-76, I—T3-77, I—T3—78, I—T3-80, I-T3-81, I—T3-84, I—T3-85, I-T3- 2014/073795 86, I-T3—87, I-T3—88, I-T3—89, I—T3-90, I—T3—9l, 2, I-T3—93, I—T3—94, I-T3-95, l-T3—96, I—T3-97, I— T3-98, l—T3-99, l-T3-100, I—T3—101, I-T3—102, l—T3—103, I—T3—104, 05, I—T3-106, I-T3-107, I-T3— 108, 09, l—T3-110, l-T3-lll, l-T3-112, l-T3—ll3, I—T3-ll4, I—T3-115, I—T3—ll6, I-T3—1l7, I-T3- 118, I—T3-1l9, l-T3-120, I—T3-123, I—T3-124, I—T3-l25, I-T3-l27, I-T3-128, I—T3-129, I-T3-130, I—T3- 131, I-T3—l32, I—T3-133, I-T3-135, I-T3-136, I—T3—137, I—T3—139, l—T3—l40, I—T3—l4l, I-T3-l43, I—T3- 145, I-T3—146, 48, I—T3-l49, I—T3-150, I-T3-151, I-T3—155, I-T3-l60, I—T3—16l, I-T3-l62, I-T3- 163, l-T3-165, I-T3—l68, I—T3—l75, 76, 89, I-T4-l, I—T4-2, I-T4-3, I-T4-4, I-T22-1, I-T22-2, I-T22-3, I-T22-4, I—T22-5, 7, I—T23-l, I—T23-2, I—T46-2 In this test, for example, the following compounds from the preparation examples show an efficacy of 95% at an application rate of 100 ppm: I-T3-l l, I-T3-17, I—T3-l9, I—T3-41, I-T3-45, 0, I-T3-79, I- T3-82, I-T3-83, I—T22-6 In this test, for example, the following compounds from the preparation examples show an efficacy of 90% at an application rate of 100 ppm: I-T3-15, I—T3-37, I—T3-60, I—T3-126, I—T3-l44 In this test, for example, the following compounds from the ation examples show an efficacy of 80% at an application rate of 100 ppm: I-T3-l3, I-T3-l6, I-T3-36 Lucilia cuprina test Solvent: dimethyl sulphoxide To produce an appropriate active ingredient formulation, 10 mg of active ingredient are mixed with 0.5 ml of yl sulphoxide, and the concentrate is diluted with water to the desired concentration.
About 20 L1 larvae of the Australian sheep blowfly (Lucilia cuprina) are transferred into a test vessel containing minced horsemeat and the active ingredient preparation of the desired concentration.
After 2 days, the kill in % is ined. 100% means that all the larvae have been killed; 0% means that none of the larvae have been . id="p-710" id="p-710" id="p-710" id="p-710" id="p-710" id="p-710"
[710] In this test, for example, the following compounds from the preparation examples show an efficacy of 100% at an application rate of 100 ppm: I-T3-l, I-T3-2, I—T3-3, I-T3-4, I—T3-5, I—T3-6, l-T3- 7, I—T3—8, I—T3—9, I—T3-10, 5, I-T3-17, I—T3—18, I-T3—20, I-T3-21, I—T3-23, I-T3-24, I-T3-25, I—T3— 26, 7, I—T3 -28, I—T3-29, 0, I-T3-31, I—T3-32, I-T3-33, I—T3-34, I-T3-35, I—T3-36, I—T3-37, I- T3—38, l—T3-39, I-T3—40, 2, I-T3-43, I-T3—44, I—T3-45, I-T3-46, l-T3-47, I-T3—48, I-T3—49, I-T3- 50, I—T3—51, I-T3—52, 3, I-T3-54, I-T3—55, I-T3-56, I—T3-57, I—T3-58, I-T3-59, l, I-T3—62, I— T3—63, I—T3-64, I-T3—65, I-T3-66, I—T3-67, I—T3—68, I—T3-70, I—T3-71, I-T3-72, I-T3—73, I-T3-77, I-T3- 78, I—T3-80, I—T3-8l, I—T3—82, 3, I-T3-84, I—T3-85, I—T3-86, I—T3-87, I-T3-88, I-T3-89, I—T3-90, I— T3—91, I—T3-92, I-T3-93, I—T3—94, I-T3-96, I—T3-97, I—T3-98, I—T3-99, I—T3-100, I-T3-101, I—T3-102, I— VVO 2015/067647 - 260 — 2014/073795 T3-103, I-T3—104, I—T3-105, I—T3—106, I—T3—107, I—T3—108, I-T3—109, I-T3—110, I-T3-lll, I-T3-112, I— T3-ll3, I—T3—ll4, I-T3—115, I-T3—ll6, I-T3-ll7, I—T3-ll8, I—T3-ll9, l—T3-l20, l-T3-l23, I-T3—l24, I— T3—l25, I—T3-l30, I-T3—13l, I-T3—133, I—T3—l36, I—T3—l39, I-T3-l40, I—T3-l4l, I—T3-l43, I-T3—144, I- T3-l45, 48, I—T3-l49, I—T3-150, I—T3-151, I—T3-155, I—T3-l60, I-T3-161, I—T3-l62, I-T3—l63, I- , I—T3—168, I-T3-l75, I—T3—l76, I-T3-189, , I—T4—2, I—T4-3, I—T4-4, l, 2, IT22-3 , 5, I—T22-6, 7, l, I-T23-2, I—T46-2 In this test, for example, the ing compounds from the preparation examples show an efficacy of 95% at an application rate of 100 ppm: I—T3—69 In this test, for example, the following compounds from the preparation examples show an efficacy of 90% at an application rate of 100 ppm: I—T3-41, I-T3-60, I—T3—74, 6, I—T3—l27, I—T3— In this test, for example, the following compounds from the preparation examples show an efficacy of 80% at an application rate of 100 ppm: 2, I—T3-75, I—T3—79, I—T3—121, I—T3-137 Musca ica test [7 14] Solvent: dimethyl sulphoxide To produce an appropriate active ingredient formulation, 10 mg of active ient are mixed with 0.5 ml of dimethyl sulphoxide, and the concentrate is diluted with water to the desired concentration.
Vessels containing a sponge treated with sugar solution and the active ingredient formulation of the desired concentration are populated with 10 adult houseflies (Musca domestica).
After 2 days, the kill in % is determined. 100% means that all of the flies have been killed; 0% means that none of the flies have been killed.
In this test, for example, the following compounds from the preparation examples show an efficacy of 100% at an ation rate of 100 ppm: I—T3-1, I-T3-2, I-T3-3, I-T3-4, , I—T3-8, I—T3- 20, 1, I—T3-23, I—T3-24, I-T3-25, I-T3-26, I—T3-27, I—T3—29, I-T3—3l, I-T3-34, I—T3-38, I—T3-42, I— T3—43, I—T3-46, I—T3—48, I—T3—52, I—T3—53, I-T3-54, I—T3-55, I-T3-56, I-T3-57, I—T3-58, I-T3—6l, I—T3— 62, I—T3—63, I—T3—64, I-T3-65, I—T3-7l, I-T3-72, I—T3—73, I—T3—77, l-T3—80, 4, I-T3-85, I-T3-86, I— T3—87, 9, I—T3—91, I-T3—92, I—T3—93, I—T3—94, I—T3-96, I-T3-97, I—T3—100, I-T3-101, I—T3—102, I— T3—103, I—T3-104, I-T3—106, I—T3-107, I-T3-108, I—T3—109, 10, I—T3—1ll, I—T3-112, I—T3—113, l- T3-ll4, I-T3—115, I—T3—116, I-T3—ll7, I-T3—118, I—T3—ll9, I—T3-120, I-T3-l23, I—T3—124, I—T3-125, I- T3-130, I-T3-131, I-T3—133, I-T3—136, I—T3-l37, I—T3—141, 43, I—T3-l44, I—T3—148, I—T3—l49, I- T3-150, I—T3-151, I—T3-155, I—T3-160, I—T3—l6l, I—T3-162, I—T3-l63, I-T3-165, I—T3-l75, I—T3-176, I— T3—189, I—T4—2, I—T22-l, I—T22—2, I-T22—3, I—T22—5, I—T22-7, I-T23—1, I-T23-2 VVO 2015/067647 — 261 — In this test, for example, the ing compounds from the preparation examples show an efficacy of 95% at an application rate of 100 ppm: I—T3-51 In this test, for example, the following nds from the preparation es show an efficacy of 90% at an application rate of 100 ppm: I-T3—30, I—T3-67, I—T3-76, I—T3-81, I—T3-90, I-T3-98, I—T3-99, I-T3-l39, I—T3-145, 6 In this test, for example, the following compounds from the preparation examples show an efficacy of 80% at an application rate of 100 ppm: I-T3-7, I-T3-66, I—T3-68, 9, I—T3-88, I—T3-105, I—T3-121, 29 In this test, for example, the following nds from the preparation examples show an efficacy of 80% at an application rate of 20 ppm: I-T3-28 In this test, for example, the ing compounds from the preparation examples show an efficacy of 80% at an application rate of 4 ppm: 5 Meloidogyne incognita test Solvent: 125.0 parts by weight of acetone id="p-725" id="p-725" id="p-725" id="p-725" id="p-725" id="p-725"
[725] To produce an appropriate active ient formulation, 1 part by weight of active ingredient is mixed with the stated amount of solvent and the concentrate is diluted with water to the desired concentration. s are filled with sand, active ingredient solution, an egg/larvae suspension of the southern root-knot nematode (Meloidogyne incognita) and lettuce seeds. The lettuce seeds germinate and the plants develop. The galls develop on the roots.
After 14 days, the nematicidal efficacy in % is determined by the ion of galls. 100% means that no galls were found; 0% means that the number of galls on the treated plants corresponds to the untreated control.
In this test, for example, the following compounds from the preparation examples show efficacy of 90% at an application rate of 20 ppm: I-T3—27, I—T3—28, I-T3-184, I—T3-185 Myzus persicae — spray test Solvent: 78 parts by weight of acetone and 1.5 parts by weight of dimethylformamide Emulsifier: alkylaryl polyglycol ether To produce an appropriate active ingredient formulation, 1 part by weight of active ingredient is dissolved using the specified parts by weight of solvent and made up with water containing an emulsifier — [Q 02- concentration of 1000 ppm until the desired concentration is attained. To produce further test concentrations, the preparation is diluted with emulsifier—containing water.
Discs of Chinese e leaves (Brassica pekinensis) infested by all stages of the green peach aphid (Myzus persicae) are sprayed with an active ingredient formulation of the d concentration.
After 6 days, efficacy in % is determined. 100% means that all the aphids have been killed; 0% means that none of the aphids have been killed.
In this test, for example, the following compounds from the preparation examples show efficacy of 100% at an application rate of 500 g/ha: I-T3-7, I—T3-20, I—T3—43, I—T3—44, I—T3—46, 2, I-T3- 100,1—T3-106, I—T3-107, I—T3-108, I—T3-110, I—T3-122, I-T3-185, I-T3-187 id="p-735" id="p-735" id="p-735" id="p-735" id="p-735" id="p-735"
[735] In this test, for example, the following compounds from the preparation es show efficacy of 90% at an application rate of 500 g/ha: I—T3-8, I—T3—21, I-T3-29, I-T3-30, I—T3-42, I—T3-91, I—T3-97, I-T3-103, I-T3-105, I-T3—109, I-T3—1 14, I—T3—l 17, I-T3—l l9, I—T3—120, 86 In this test, for example, the following compounds from the preparation examples show efficacy of 100% at an application rate of 100 g/ha: I-T3-1, I—T3—3, 7, I—T3—54, I—T3-55, I—T3-77, I—T3-88, I-T3-99, I-T3-101, I-T3-112, I—T3—113, I-T3—115, I—T3-116, I—T3—118, I-T3-120, 23, I-T3-124, IT3-125 , I—T3-127, I—T3-128, I-T3-129, I—T3-130, I—T3-162, I—T3-165, I—T3-l70, I—T3-174, I—T3-175, I— T3—l76, I-T3-179, I-T3-184, I-T3-l89, I-T22-l, I-T22-2, I-T22-5, I-T22—7 In this test, for e, the following compounds from the preparation es show efficacy of 90% at an application rate of 100 g/ha: I-T3-28, I-T3-38, I—T3-39, I—T3-53, I—T3-64, I-T3-72, I—T3—76, I-T3-80, I—T3-81, I-T3-85, I—T3-87, I—T3-95, I—T3-96, I-T3—98, I—T3-131, I—T3-132, I—T3-145, I-T3-l60, I—T3-164, I-T3-163, I-T4-3 [73 8] In this test, for example, the ing compounds from the preparation examples show efficacy of 90% at an application rate of 20 g/ha: I—T3-182, I—T4-2 Phaedon cochleariae — spray test id="p-739" id="p-739" id="p-739" id="p-739" id="p-739" id="p-739"
[739] Solvent: 78.0 parts by weight of acetone and 1.5 parts by weight of dimethylforrnamide fier: alkylaryl ycol ether To produce an appropriate active ingredient ation, 1 part by weight of active ingredient is dissolved using the specified parts by weight of solvent and made up with water containing an emulsifier concentration of 1000 ppm until the desired concentration is attained. To produce further test concentrations, the preparation is d with emulsifier-containing water. "’0 20157067647 - 263 — Discs of Chinese cabbage leaves (Brassica nsis) are sprayed with an active ingredient formulation of the desired concentration and, after drying, populated with larvae of the mustard beetle on cochleariae).
After 7 days, efficacy in % is determined. 100% means that all the beetle larvae have been killed; 0% means that no beetle larvae have been killed.
In this test, for e, the following compounds from the ation examples show efficacy of 100% at an application rate of 500 g/ha: I-T3-7, I-T3-8, I-T3-9, I—T3-10, 2, I-T3-15, I-T3-17, I- T3—18, I-T3-19, I-T3-20, I-T3-21, I-T3-22, I—T3-23, I—T3—24, 5, 6, 9, I-T3-30, I—T3- 31, I-T3-34, I—T3-35, I—T3-36, I-T3-37, I—T3—42, I-T3—43, I-T3-44, I—T3-45, 6, I—T3-47, I-T3-65, I- T3-66, I—T3—67, I-T3—68, I-T3-69, I—T3-70, I—T3-73, I—T3-74, I—T3-75, I-T3-76, I—T3—77, I-T3-78, I-T3- 79, I-T3—89, I—T3-90, I-T3—91, I—T3-92, I—T3-96, I—T3-97, I—T3-98, I—T3-100, 01, I—T3-102, I-T3- 103, I-T3-104, I-T3—105, 06, I—T3-107, I-T3-108, 09, I—T3-110, I-T3-111, I-T3—112, I—T3- 113, I—T3-114, I—T3-115, I—T3-116, I—T3-117, I-T3-118, I-T3-119, I—T3-120, I—T3-126, I-T3-184, I-T3- 185, I-T3-186, I-T3—187, I—T3—188, I-T23—1,I-T23-2 id="p-745" id="p-745" id="p-745" id="p-745" id="p-745" id="p-745"
[745] In this test, for example, the following compounds from the preparation examples show efficacy of 100% at an application rate of 100 g/ha: I—TZ-l, I-T2-2, I—T3—1, I-T3—2, I-T3-3, I-T3—4, I—T3—5, I-T3—6, I—T3-27, I-T3—28, I-T3—38, I—T3-39, I—T3-40, I—T3-41, I-T3-48, I-T3-49, 0, I-T3-51, I—T3-52, I-T3- 53, I-T3-54, I-T3 -55, I-T3—56, I-T3-57, I-T3-58, I-T3-59, I—T3-61, I—T3-62, I—T3—63, I-T3-64, I-T3-71, I- T3-72, I-T3-80, I—T3-81, I—T3-82, I-T3—83, I—T3—84, I—T3-85, I-T3-86, I-T3-87, 8, I-T3-93, I—T3- 94, I-T3-95, I-T3-99, I—T3-123, I—T3-124, I-T3-125, I-T3-127, 28, I-T3-129, I—T3-130, I—T3-131, I-T3-132, 33, I—T3-136, I—T3—137, I—T3—139,I-T3—140,I—T3-141,I-T3-143,I—T3-144, I-T3-145, I— T3-148, I—T3-149, I—T3-151, I—T3-152, 53, I-T3-155, 60, I-T3-161, I—T3—162, I-T3-163, I- T3-164, I-T3-165, I-T3-168, I—T3-169, I-T3-170, I—T3—171, I—T3-172, I—T3—174, I-T3—175, I—T3—176, I— T3-177, I—T3-178, 79, I—T3—180, I—T3—181, I-T3—182, I-T3—183, I-T3—189, I—T3—190, I—T3—191, I— T3-192, I—T3-l95, I—T3-197, 98, I—T3—220, 21, I-T3—222, I-T3-223, I-T4-1, I-T4-2, I-T4-3, I-T4-4, I-T22-1, I-T22-2, I-T22—3, I-T22-4, I-T22-5, I—T22-6, I-T22-7, I-T46—2, I-T46-3, I—T46-4, I—T46- , I-T46-6 In this test, for example, the following compounds from the preparation examples show efficacy of 83% at an application rate of 100 g/ha: I-T3-138 3O Spodoptera frugiperda — spray test Solvent: 78.0 parts by weight of acetone and 1.5 parts by weight of dimethylformamide Emulsifier: ryl polyglycol ether To produce an appropriate active ingredient formulation, 1 part by weight of active ingredient is dissolved using the specified parts by weight of solvent and made up with water containing an emulsifier VV’O 2015/067647 — 264 — concentration of 1000 ppm until the desired concentration is attained. To produce r test concentrations, the preparation is diluted with emulsifier-containing water.
Leaf discs of maize (Zea mays) are sprayed with an active ingredient formulation of the desired concentration and, after drying, populated with caterpillars of the armyworrn (Spodoptera frugzperda).
After 7 days, y in % is determined. 100% means that all the caterpillars have been killed; 0% means that no caterpillars have been killed.
In this test, for example, the following compounds from the preparation examples show y of 100% at an application rate of 500 g/ha: I—T3-7, I-T3-8, , I-T3-10, I-T3-l2, I-T3-l7, I—T3-18, I— T3-l9, I-T3-20, I-T3-21, I—T3-22, I—T3-23, I-T3—24, I-T3—25, I-T3-26, I—T3-29, I-T3-30, I-T3-31, I—T3- 34, I—T3-42, I-T3-43, I—T3—44, I-T3-45, 6, 7, 5, I-T3—66, I—T3—67, I—T3-68, I—T3-69, I- T3-70, I-T3—73, I-T3—74, I—T3-75, I—T3-76, I-T3—77, I—T3—78, I—T3-79, I—T3-89, I-T3—90, I-T3—91, I-T3- 92, I—T3-96, I—T3-97, I-T3—98, I-T3-100, I—T3-102, I-T3—103, I-T3—104, I—T3-105, I—T3—106, I-T3—107, I— T3—108, I—T3-109, I—T3—110, I-T3-lll, I-T3-112, I—T3-ll3, I—T3-1l4, I—T3—115, I—T3-116, I—T3-ll7, I- ,I-T3-119, 20,I—T3—126,I-T3—l84,I—T3-185,I-T3—186,I—T3-187,I-T23—1,I-T23-2 id="p-753" id="p-753" id="p-753" id="p-753" id="p-753" id="p-753"
[753] In this test, for example, the following nds from the preparation examples show efficacy of 83% at an application rate of 500 g/ha: I-T3-101 In this test, for example, the ing compounds from the preparation examples show efficacy of 100% at an application rate of 100 g/ha: I-T2—2, I-T3—l, I-T3—2, I—T3-3, I-T3-4, I—T3—27, I-T3-28, I- T3-38, I—T3-39, I-T3—40, I—T3—4l, I-T3-48, I—T3-52, I-T3-53, I-T3—54, I-T3-55, I-T3-56, I—T3-57, I-T3— 58, I-T3—6l, I—T3-62, I—T3—63, I—T3-64, I-T3—71, I—T3-72, I-T3-80, I—T3-81, I-T3—82, I-T3—83, I-T3—84, I- T3-85, I—T3-86, I—T3—87, I-T3-88, I—T3—93, I-T3-94, 5, I—T3-99, I—T3—123, I—T3—124, 25, I- T3-130, I-T3-l31, I-T3-133, I—T3-136, I-T3-137, I-T3-138, I-T3-139, I—T3-l40, I-T3-14l, I—T3-143, I- T3-145, I-T3—l48, I—T3-151, I—T3-152, I—T3—155, 60, I—T3-l61, I—T3—l62, I—T3-163, I—T3-164, I- T3-l65, I-T3—170, I—T3-l74, I—T3-175, I—T3—176, I-T3-l89, I—T3-l9l, I—T3—l92, I-T3—l97, I-T3-198, I- T4-1, I—T4-2, I-T4-3, I—T4-4, 1, I-T22-2, I—T22—3, 5, 7, I—T46-2, 3, I-T46—4, IT46-5 , I-T46—6 In this test, for example, the ing compounds from the preparation examples show efficacy of 83% at an application rate of 100 g/ha: I—T3-35, 0, I—T3-l69, I-T3—l77 Tetranychus urticae — spray test, OP-resistant [75 6] t: 78.0 parts by weight of acetone and 1.5 parts by weight of dimethylformamide Emulsifier: alkylaryl polyglycol ether [75 8] To produce an appropriate active ingredient formulation, 1 part by weight of active ingredient is dissolved using the specified parts by weight of solvent and made up with water containing an emulsifier ‘NO 67647 - [\J O\ 5 — 2014/073795 concentration of 1000 ppm until the desired concentration is attained. To produce fuither test concentrations, the preparation is diluted with emulsifier-containing water.
Discs of bean leaves (Phaseolus vulgaris) infested by all stages of the greenhouse red spider mite (Tetranychus e) are sprayed with an active ingredient formulation of the desired concentration.
After 6 days, efficacy in % is determined. 100% means that all the spider mites have been killed; 0% means that none of the spider mites have been killed.
In this test, for e, the following compounds from the preparation examples show an efficacy of 100% at an application rate of 500 g/ha: , I—T3—8, I-T3—9, 0, I—T3-20, I—T3-21, I- T3-22, I—T3-23, I—T3-24, I—T3-26, I—T3-29, I-T3-30, I-T3-31, I—T3-34, I—T3-42, I—T3-43, I—T3—44, I—T3- 45, I-T3—46, I—T3—47, I-T3-69, I-T3—75, I—T3-76, 7, I—T3—78, I-T3-91, I-T3-92, I—T3-96, I—T3—97, I- T3-98, I—T3-100, I—T3-101, I-T3—103, 06, I-T3—107, I-T3—108, I—T3-109, I-T3—110, I-T3-112, I- T3—113, I-T3—114, I-T3-115, I-T3-119, I-T3-120, 84, I—T3-185, I—T3-186, I—T3-187, I—T23-1, I- T23—2 id="p-762" id="p-762" id="p-762" id="p-762" id="p-762" id="p-762"
[762] In this test, for example, the following compounds from the ation examples show an efficacy of 90% at an application rate of 500 g/ha: I—T3-25, 5, I-T3-70, I—T3-89, I—T3-90, I-T3— 102, I—T3-104, I—T3-105, 16, I-T3-117, I-T3-118 In this test, for example, the following compounds from the preparation examples show an efficacy of 100% at an application rate of 100 g/ha: I—T3-1, I—T3-2, I—T3-3, I—T3-4, I—T3—27, I-T3-28, I- T3-38, 9, I—T3-41, I-T3-51, I-T3-53, I—T3-54, I—T3-55, I—T3—56, I-T3-57, I-T3-58, I—T3-61, I—T3- 62, 3, I-T3-64, I-T3-72, I—T3-73, 0, I—T3-81, I—T3-82, I—T3—83, I—T3—84, I—T3-85, I—T3-86, I- T3-87, I—T3-88, I-T3-93, I—T3-94, I—T3-95, I—T3-99, I—T3-124, I—T3-125, I—T3-127, 29, I—T3-130, I—T3-131, I—T3-132, I—T3—133,I—T3-139,I—T3—145, I-T3—146, I-T3-155, I—T3-160, I-T3-161, I—T3-162, I- T3-163, I—T3-164, I—T3-165, I—T3-168, I—T3-169, I-T3-170, I-T3—174, I-T3-175, I-T3-176, 77, I- T3-178, I—T3-179, I—T3-l80, I—T3-181, I—T3—182, I—T3-183, I—T3—189, I—T3-190, I—T3-192, I—T3-197, I— T3-221, I—T3-222, I—T3-223, I-T4-1, I—T4-2, I-T4-3, I-T4-4, I-T22—4, I—T22-5, I—T22-7, I—T46-4, I-T46-5, I-T46-6 In this test, for e, the ing compounds from the preparation examples show an y of 90% at an application rate of 100 g/ha: I—T3—50, I—T3—52, I-T3-71, I—T3-74, I—T3-111, I-T3— 123, I-T3—137, I-T3—138, I—T3—147, I-T3—148, I—T3-151, I—T3-172, 95, I-T22-l, I—T22—2, I—T22—3 In this test, for example, the following compounds from the preparation examples show an efficacy of 100% at an application rate of 20 g/ha: I—T3-49 VVO 2015/067647 — 266 - Anopheles test (ANPHGB surface treatment) Solvent: e + 2000 ppm rapeseed oil methyl ester (RME) To produce an appropriate active ingredient formulation, the active ingredient is dissolved in the solvent (2 mg/ml). The active ingredient formulation is pipetted onto a glazed tile and, after it has dried off, adult toes of the species Anopheles gambiae strain RSPH (homozygot kdr) are placed onto the d tile. The exposure time is 30 s. 24 hours after contact with the treated surface, mortality in % is determined. 100% means that all mosquitoes have been killed; 0% means that none of the mosquitoes have been killed.
In this test, for example, the following compounds from the ation examples show efficacy of 90-100% at an application rate of 100 mg/mz: I—T3-20, I-T3-24, I-T3-27, I—T3-28, I—T3-43, I-T3-52, I- T3—53, I-T3-54, I—T3-56, I-T3-57, I-T3-61, I—T3-100, I—T3-102, l—T3-112, I—T3-123, I—T3—130, I—T3-133, I—T3-134, I—T3-136, 45, l-T3—148, I-T3-155, I—T3—160, I-T3-162, I—T3—173, l-T3—189, I—T22—1 In this test, for example, the following compounds from the preparation examples show efficacy of % at an application rate of 20 mg/m2: l-T3-23, I-T3-24, I—T3-26, I—T3-27, I—T3-28, I-T3-43, l— T3-52, I-T3-53, 4, I-T3-57, I-T3-58, I-T3-61, I—T3—87, I—T3-91, 2, I-T3-100, I-T3-102, I- , I—T3-112, I—T3-116, I—T3-130; I-T3-133, I-T3-134, I-T3-136, I—T3-137, I—T3-145, 48, I- T3-155, I-T3—159, I—T3-160, l-T3-162, I—T3-189, I-T22-2 Anopheles test (ANPHFU surface treatment) Solvent: acetone + 2000 ppm rapeseed oil methyl ester (RME) id="p-772" id="p-772" id="p-772" id="p-772" id="p-772" id="p-772"
[772] To produce an appropriate active ingredient formulation, the active ingredient is dissolved in the solvent (2 mg/ml). The active ingredient formulation is pipetted onto a glazed tile and, after it has dried off, adult toes of the species Anopheles funestus strain FUMOZ-R (Hunt et al., Med Vet Entomol. 2005 Sep; 19(3):271—5) are placed onto the treated tile. The exposure time is 30 minutes. 24 hours after contact with the treated surface, ity in % is determined. 100% means that all mosquitoes have been killed; 0% means that none of the mosquitoes have been killed.
In this test, for example, the following compounds from the preparation examples show efficacy of 90—100% at an application rate of 100 mg/mz: 4, I-T3-25, l-T3-3 8, I—T3-43, I—T3—46, I-T3-54, l- T3-56, I—T3—58, 3, I-T3—86, 2, I—T3-99, I-T3—100, I-T3-102, I~T3-107, I-T3-112, l-T3-113, I—T3-115, I-T3-123, I-T3-133, I-T3-134, I-T3—136, I-T3-145, l-T3-148, I—T3—155, l—T3-159, 60, I- T3-162, 89, 1, I-T22-2 In this test, for example, the following compounds from the preparation examples show efficacy of 90—100% at an application rate of 20 mg/m2: l-T3-3, l-T3—24, I-T3—25, L3 —26, I—T3—3 8, I—T3-42, I—T3- 2014/073795 43, I—T3—46, l-T3—52, I—T3-53, 4, I—T3-55, I—T3-57, l, I-T3—63, I—T3-92, I—T3—93, I-T3—99, I— T3-100, I—T3-102, 07, I—T3—112, l-T3—ll3, l—T3-ll6, l-T3—123, I-T3-l34, l—T3-l36, 45, I— T3—148,I-T3-155,I—T3-159,I-T3—160,I-T3-162,I-T3—l89,I-T22—1,I-T22—2,I—T23—1,I-T23-2 Aedes test (AEDSAE surface treatment) Solvent: acetone + 2000 ppm rapeseed oil methyl ester (RME) To produce an appropriate active ient formulation, the active ingredient is dissolved in the t (2 mg/ml). The active ingredient formulation is ed onto a glazed tile and, after it has dried off, adult mosquitoes of the species Aedes aegypti strain MONHEIM are placed onto the treated tile.
The exposure time is 30 minutes. id="p-778" id="p-778" id="p-778" id="p-778" id="p-778" id="p-778"
[778] 24 hours after contact with the treated surface, mortality in % is determined. 100% means that all mosquitoes have been killed; 0% means that none of the mosquitoes have been killed.
In this test, for example, the ing compounds from the preparation examples show efficacy of 90-100% at an application rate of 100 mg/mz: I-T3-l, I-T3-3, I—T3-8, I-T3 ~20, I-T3-2l, I—T3-23, I—T3- 24, I-T3 -25, I-T3—27, I-T3—28, I—T3-38, I-T3 -42, I—T3-43, I—T3-46, I-T3-52, I-T3—53, I-T3-54, I-T3-55, I- T3—56, I-T3-57, I-T3-58, I—T3—61, I—T3-63, I—T3—64, I-T3—86, I-T3-87, I—T3-9l, I-T3—92, I-T3—93, I-T3- 96, I-T3-98, 9, I-T3-100, 01, 02, I-T3-103, I-T3-106, 07, I-T3—108, I-T3—112, I-T3-113,I—T3—115,I-T3—ll7,I-T3-118,I—T3—120,I-T3-123,I-T3-130,I-T3—l33,I—T3-134, I-T3-136,1— T3-145, I—T3-148, I—T3-155, I—T3—160, I—T3—162, I—T3-163, I—T3—173, I—T3-189, I—T22—1, I-T22-2, I- T23-l, I-T23-2 id="p-780" id="p-780" id="p-780" id="p-780" id="p-780" id="p-780"
[780] In this test, for example, the following compounds from the preparation examples show efficacy of 90-100% at an application rate of 20 mg/m2: I-T3—1, I-T3-3, I—T3-8, I-T3-20, I-T3-21, I-T3-23, I—T3- 24, I—T3-25, I-T3-27, I—T3-28, I—T3-38, I-T3-42, I-T3-43, I—T3—46, I-T3-52, I—T3-53, 4, I-T3-55, IT3-56 , I-T3—57, I—T3-58, I-T3-61, I-T3-63, I-T3-64, I-T3-86, I—T3-87, I-T3-91, I-T3-92, I—T-93, I-T3-95, I-T3-96, I—T3—98, I-T3-99, I—T3—100, I—T3-101, I-T3—102, I—T3—103, I-T3-106, I—T3-107, I-T3-108, I-T3- 112, I-T3-113, I-T3—115, I-T3—1 16, I-T3-117, 18, 23, I-T3-130, I—T3-133, I—T3—l34, I-T3- 136, I—T3-145, I-T3-148, I—T3—155, I-T3-159, I-T3-160, I-T3-162, I—T3-l63, I—T3-l73, I-T3-189, I-T22- 1, I—T22-2, 1, I-T23-2
NZ719644A 2013-11-05 2014-11-05 Substituted benzamides for the treatment of arthropods NZ719644B2 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
EP13191610.8 2013-11-05
EP13191610 2013-11-05
EP14181149.7 2014-08-15
EP14181149 2014-08-15
PCT/EP2014/073795 WO2015067647A1 (en) 2013-11-05 2014-11-05 Substituted benzamides for the treatment of arthropods

Publications (2)

Publication Number Publication Date
NZ719644A NZ719644A (en) 2021-06-25
NZ719644B2 true NZ719644B2 (en) 2021-09-28

Family

ID=

Similar Documents

Publication Publication Date Title
JP6840803B2 (en) Substituted benzamides for treating arthropods
AU2014345595B2 (en) Novel compounds for combating arthropods
US10273226B2 (en) Pyrazolyl-heteroarylamides as pesticides
NZ719644B2 (en) Substituted benzamides for the treatment of arthropods
NZ719646B2 (en) Substituted benzamides for treating arthropodes
OA18534A (en) Substituted benzamides for treating arthropodes.
HK1223099B (en) Compounds for treating arthropodes
HK1227029B (en) Substituted benzamides for the treatment of arthropods