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NZ739774B2 - Method for the preparation of (4s)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1-6-naphthyridine-3-carboxamide and the purification thereof for use as an active pharmaceutical ingredient - Google Patents
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NZ739774B2 - Method for the preparation of (4s)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1-6-naphthyridine-3-carboxamide and the purification thereof for use as an active pharmaceutical ingredient - Google Patents

Method for the preparation of (4s)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1-6-naphthyridine-3-carboxamide and the purification thereof for use as an active pharmaceutical ingredient

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Publication number
NZ739774B2
NZ739774B2 NZ739774A NZ73977416A NZ739774B2 NZ 739774 B2 NZ739774 B2 NZ 739774B2 NZ 739774 A NZ739774 A NZ 739774A NZ 73977416 A NZ73977416 A NZ 73977416A NZ 739774 B2 NZ739774 B2 NZ 739774B2
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NZ
New Zealand
Prior art keywords
formula
compound
xviii
xvi
preparing
Prior art date
Application number
NZ739774A
Other versions
NZ739774A (en
Inventor
Johannes Platzek
Original Assignee
Bayer Pharma Aktiengesellschaft
Filing date
Publication date
Application filed by Bayer Pharma Aktiengesellschaft filed Critical Bayer Pharma Aktiengesellschaft
Priority claimed from PCT/EP2016/069558 external-priority patent/WO2017032673A1/en
Publication of NZ739774A publication Critical patent/NZ739774A/en
Publication of NZ739774B2 publication Critical patent/NZ739774B2/en

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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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    • A61P5/42—Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of mineralocorticosteroids
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    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Abstract

The present invention relates to a novel and improved method for the preparation of (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1-6-naphthyridine-3-carboxamide of the formula (I) and of a crystalline modification of said compound.

Claims (13)

The claims defining the invention are as follows:
1. Process for preparing the compound of the formula (I) wherein the racemic compound of the formula (XIII) is separated into its enantiomers, and 5 the compound of the formula (XIII) H N N is prepared by reacting the compound of the formula (XVIII) H N NH XVIII with the orthoester (XX) 10 (XX) where R may be H or methyl
2. Process according to claim 1 for preparing the compound of the formula (I) 5 wherein the racemic compound of the formula (XIII) is separated into its enantiomers, where the compound of the formula (XIII) H N N is prepared by reacting the compound of the formula (XVIII) H N NH XVIII 10 with the orthoester (XX) where R may be H or methyl, and the compound of the formula (XVIII) H N NH H C N (XVIII), 5 is prepared by reacting the compounds of the formula (XVI a+b) XVI a+b with the compound of the formula (IX) 10
3. Process according to claim 1 or 2 for preparing the compound of the formula (I) wherein the racemic compound of the formula (XIII) is separated into its enantiomers, where the compound of the formula (XIII) H N N 5 is prepared by reacting the compound of the formula (XVIII) H N NH XVIII with the orthoester (XX) where R may be H or methyl, and 10 the compound of the formula (XVIII) (XVIII), is prepared by reacting the compounds of the formula (XVI a+b) XVI a+b with the compound of the formula (IX) the compound of the formula (XVI a+b) is prepared by reacting the compound of the formula (VI) with the compound of the formula (XVII) (XVII). 5
4. Process for preparing the compound of the formula (I) O O CH H N N H C N using the compound of the formula (XVIII) H N NH H C N (XVIII).
5. Process for preparing the compound of the formula (I) H N N 10 (I), using the compounds of the formula (XVI a+b) XVI a+b
6. Process according to claim 4 or 5 for preparing the compound of the formula (I) 5 using the compound of the formula (XVIII) (XVIII) and the compounds of the formula (XVI a+b) XVI a+b
7. Compound of the formula H N NH H C N (XVIII), 5 or a salt, solvate or solvate of a salt thereof.
8. Compound of the formula (XVIa+b) as an E/Z mixture XVI a+b or a salt, solvate or solvate of a salt thereof.
9. Process for preparing the compound of the formula (XVIII) H N NH (XVIII), wherein the compounds of the formula (XVI a+b) XVI a+b 5 are reacted with the compound of the formula (IX)
10. Process for preparing the compounds of the formula (XVI a+b) XVI a+b wherein the compound of the formula (VI) is reacted with the compound of the formula (XVII) (XVII)
11. Process for preparing the compound of the formula (XIII) H N N 10 wherein the compound of the formula (XVIII) H C N (XVIII), is reacted with the orthoester (XX) 5 where R may be H or methyl.
12. Process according to claim 11 for preparing the compound of the formula (XIII) H N N wherein the compound of the formula (XVIII) H C N (XVIII), is reacted with the orthoester (XX) where R may be H or methyl, and 5 wherein the compound of the formula (XVIII) is prepared by reacting the compounds of the formula (XVI a+b) XVI a+b with the compound of the formula (IX) 10
13. Process according to any one of claims 1 to 6 for preparing the compound of the formula (I), wherein the compound of formula (I) is a crystalline polymorph I H N N wherein the compound of the formula (I), present in one or more polymorphs or as a solvate in a solvent, is stirred at a temperature of 20°C - 120°C and the compound of the formula (I) is isolated in crystalline polymorph I, wherein the solvent is selected from the group consisting of methanol, ethanol, acetonitrile and mixtures thereof.
NZ739774A 2016-08-18 Method for the preparation of (4s)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1-6-naphthyridine-3-carboxamide and the purification thereof for use as an active pharmaceutical ingredient NZ739774B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP15182043 2015-08-21
PCT/EP2016/069558 WO2017032673A1 (en) 2015-08-21 2016-08-18 Method for the preparation of (4s)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1-6-naphthyridine-3-carboxamide and the purification thereof for use as an active pharmaceutical ingredient

Publications (2)

Publication Number Publication Date
NZ739774A NZ739774A (en) 2025-06-27
NZ739774B2 true NZ739774B2 (en) 2025-09-30

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