JPH0710845B2 - Pyridinecarboxamide compound - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to 1,4-dihydro-2,6-dimethyl-4-oxo-
The present invention relates to a novel compound belonging to 3-pyridinecarboxamide. The compound of the present invention shows a growth inhibitory action on plants and also has an anti-inflammatory action.

(Prior Art) Conventionally, 1,4-dihydro-2,6-dimethyl-4-oxo-3
Descriptions of the compounds belonging to the pyridinecarboxamide can be found in the literature. Kato Tetsuzo, etc .: Pharmaceutical Journal, 101, 40 (1981), N- (4-chlorophenyl) -1,4-dihydro-2,6-dimethyl-4-oxo-3.
-Pyridinecarboxamide, 1,4-dihydro-2,6-dimethyl-4-oxo-N-phenyl-1- (phenylmethyl) -3-pyridinecarboxamide, 1,4-dihydro-
N- (4-methoxyphenyl) -2,6-dimethyl-4-
Four of oxo-1- (phenylmethyl) -3-pyridinecarboxamide and N- (4-chlorophenyl) -1,4-dihydro-2,6-dimethyl-4-oxo-1- (phenylmethyl) -3-pyridinecarboxamide Although compounds have been reported, this document relates to the reactivity of ketene derivatives and does not mention in what field these compounds are used. Also, Canadian Patent No. 1,115,278 (and JB Pierce et al. J. Med. Chem.
25, 131 (1982)) has an anti-inflammatory effect.
Descriptions of pyridone compounds are found, and 1,4-dihydro-2,6-dimethyl-4-oxo-N-, 1-diphenyl-3-pyridinecarboxamides, N, 1-dibutyl-1,4
-Dihydro-2,6-dimethyl-4-oxo-3-pyridinecarboxamide, N, 1-didodecyl-1,4-dihydro-
2,6-Dimethyl-4-oxo-3-pyridinecarboxamide and N- (4-chlorophenyl) -1-ethyl-
1,4-dihydro-2,6-dimethyl-4-oxo-3-pyridinecarboxamide and the like are disclosed.

On the other hand, as a compound showing activity as a plant growth regulator, particularly a chemical mating agent, 1,4-dihydro-4-oxo-3-
Although derivatives of pyridinecarboxylic acid are known,
52-144676, JP-A-57-114573), a plant growth inhibitor containing a 1,4-dihydro-2,6-dimethyl-4-oxo-3-pyridinecarboxamide compound as an active ingredient, such as compound (I), It was unknown.

The present invention provides a group of novel compounds belonging to the 1,4-dihydro-2,6-dimethyl-4-oxo-3-pyridinecarboxamide compound.

(Object and Structure) The present invention provides a compound represented by the following formula (I) and an addition salt thereof.

[Wherein R is-(CH ₂ ) n-R ₁ (n is an integer of 1 to 3; R ₁ is a lower alkoxy group, a C _{3 to} C ₁₁ alkyl group, a lower alkenyl group, a 5 or 6-membered different item) A ring group or an aryl group substituted with 1 to 2 substituents of a halogen atom, lower alkyl and lower alkoxy); R ₂ and R ₃ are benzene ring 3,4
Alternatively, they are bonded to the 5-position and are the same or different and each represents a hydrogen atom, a halogen atom, a nitro group, a lower alkyl group, a halogenated lower alkyl group or a lower alkoxy group. In the present invention, the term “lower” used for a lower alkyl group, a lower alkoxy group and the like means a group containing a C _{1 to} C ₅ carbon atom. Specific examples include lower alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl and isopentyl, and lower alkoxy groups such as methoxy, ethoxy, propoxy, isopropoxy and butoxy.

In addition, the lower alkenyl group includes vinyl, allyl, isopropenyl, 2-butenyl, 1,3-butadienyl, 2-pentenyl, 1,4-pentadienyl, 1,6-heptadienyl, 1-hexenyl and the like.

Substituted aryl groups include substituted phenyl or substituted naphthyl groups. However, the substituent is a halogen atom, a lower alkyl group and / or a lower alkoxy group.

Halogen atoms include chlorine, bromine or fluorine atoms.

The 5- or 6-membered heterocyclic group includes a nitrogen atom, an oxygen atom,
Included are 5 or 6 membered heterocycles containing 1 to 3 heteroatoms selected from sulfur atoms. Examples thereof include 5-membered ring groups such as furyl, tetrahydrofuryl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl and pyrazolyl; and 6-membered rings such as pyridyl, pyrimidinyl, pyrazinyl and pyridazinyl. These groups may be substituted with an alkyl group such as methyl or ethyl, a halogen atom or a phenyl group. When substituted with a phenyl group, it may combine with two carbon atoms in the ring to form a fused ring. Examples of the case where a condensed ring is formed include benzothiazolyl, benzofuryl, quinazolinyl, quinoxalinyl groups and the like.

When the compound of formula (I) of the present invention shows basicity, it is an addition salt with an acid such as hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, paratoluenesulfonic acid, trifluoroacetic acid, or a carboxyl group in the molecule. May form an addition salt with an inorganic base. Such addition salts are also included in the scope of the present invention.

The compounds of formula (I) of this invention can be made by the following methods.

(Method A) [Wherein R, R ₂ and R ₃ in the formula (II) are the same as the definition in the formula (I)] This method is carried out by using the 3-aminocrotonic acid anilide derivative (I
I) and 2,2,6-trimethyl-4H-1,3-dioxin-4-
It is carried out by reacting the on with a suitable solvent (eg, toluene, xylene, etc.) under heating (eg, about 100 ° C. to 140 ° C.). Here, using 2-ethyl-2,6-dimethyl-4H-1,3-dioxin-4-one instead of 2,2,6-trimethyl-4H-1,3-dioxin-4-one Is also possible. Moreover, in carrying out this method, the 3-aminocrotonic acid anilide derivative (II) is
It is not necessary to use the isolated substance and the formula RNH ₂ (III) (In the formulas (III) and (IV), R, R ₂ and R ₃ are the same as defined in the formula (I)), and the reaction mixture as it is may be directly used. In fact,
It is more convenient to use this reaction mixture.

(Method B) (In the formulas (V) and (III), R, R ₂ and R ₃ are the same as the definition of the formula (I)) This method is carried out by using the 4-pyrone compound (V) corresponding to the formula (I), namely 2, 6-dimethyl-4-oxo-N-phenyl-4H-pyran-3-carboxamide and an amine represented by the formula (III) or a salt thereof in a suitable solvent (eg, ethanol, water) at room temperature to 60 ° C. The reaction is carried out at a temperature as high as that. The amount of amine used is equimolar or more with respect to the 4-pyrone compound, and if necessary, a large excess amount is used. When the amine is available as a salt, it is necessary to provide the amine in the free form with a neutralizing amount or more of an organic or inorganic base.

(Method C) (R, R ₂ and R _{3 in} formulas (VI) and (VII) are the same as defined in formula (I))
-Dihydro-2,6-dimethyl-4-oxo-3-pyridinecarboxylic acid derivative (VI) and aniline derivative (VII) are reacted in the presence of a dehydration condensation agent. When this method is actually carried out, for example, the method described in JP-A-52-57102, which uses a 1-substituted-2-halopyridinium salt and a tertiary amine as a dehydration condensation agent, can be advantageously used.

The present invention will be described below with reference to examples. In addition, the inhibitory effect of the compounds of this invention on plant growth is shown in Reference Examples.
In addition to the compounds shown in the examples, specific names of the compounds of interest included in the present invention include 1-butyl-1,4
-Dihydro-2,6-dimethyl-N- (3,5-dimethylphenyl) -4-oxo-3-pyridinecarboxamide.

Production Example 1 1- (4-Fluorophenylmethyl) -1,4-dihydro-2,6-dimethyl-4-oxo-N-phenyl-3-pyridinecarboxamide (Method A) 2.53 g (14.3 mmol) of acetoacetanilide, 1.79 g (14.3 mmol) of 4-fluorobenzylamine and 20 m of toluene
The mixture of 1 was heated to reflux for 1.5 hours, during which the water formed was distilled off together with about 6 ml of toluene. While continuing heating, a solution of 5.10 g (35.8 mmol) of 2,2,6-trimethyl-4H-1,3-dioxin-4-one in toluene (10 ml) was added dropwise over about 30 minutes and heated for another 20 minutes. After continuing the reflux, the reaction mixture was allowed to cool to room temperature. The generated crystals were separated by filtration, washed, and dried under reduced pressure to give the title compound (2.04 g). Melting point 186-188 [deg.] C.

Production Example 2 N- (4-chlorophenyl) -1,4-dihydro-1-
(3-Methoxypropyl) -2,6-dimethyl-4-oxo-3-pyridinecarboxamide (Method B) N- (4-chlorophenyl) -2,6-dimethyl-4-oxo-4H-pyran-3-carboxamide (melting point 201-202
℃) 2.78 g (10.0 mmol) ethanol 50 ml and water 10 ml
0.98 g (11.0 mmol) of 3-methoxypropylamine and 0.7 g of sodium carbonate were added to the solution dissolved in the mixture of, and the mixture was stirred at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure, 100 ml of ethyl acetate was added to the obtained residue to dissolve it, and the solution was mixed with water,
Then, the mixture was washed with saturated aqueous sodium hydrogen carbonate, the organic layer was dried and concentrated according to a conventional method, and the residue was crystallized from ethyl acetate to give the title compound (3.13 g, yield 79%). Melting point 164-16.5 ° C.

Production Example 3 1- (4-chlorophenylmethyl) -1,4-dihydro-
2,6-Dimethyl-4-oxo-N-phenyl-3-pyridinecarboxamide (Method C) 1- (4-chlorophenylmethyl) -1,4-dihydro-
2,6-dimethyl-4-oxo-3-pyridinecarboxylic acid
Chloroform 100 was added to 2.92 g (10.0 mmol) and 2-chloro-1-methyl-pyridinium tosylate (3.60 g, 12 mmol).
After dissolving in ml, 2.43 g (24 mmol) of triethylamine was added, and the mixture was stirred at room temperature for 30 minutes. Further, 0.93 g (10 mmol) of aniline was added to the reaction mixture, and stirring was continued at room temperature for 4 hours. The reaction mixture was transferred to a separatory funnel, washed with saturated aqueous sodium hydrogen carbonate, and the organic layer was dried and concentrated by a conventional method to give 4.5 g of an oily substance. This was dissolved in about 20 ml of hot toluene and cooled to room temperature to give 1.17 g of the title compound as crystals. Melting point 246-248 ° C.

Tables 1 and 2 listed below summarize the physical properties and the like of the compounds according to the present invention.

The "performance evaluation" in Table 2 is as follows.

Talc (50 parts by weight), Bentonite (25 parts by weight) Sorpol-9047 (2 parts by Toho Chemical), Solpol-50
39 (same as above, 3 parts by weight) was mixed to prepare a carrier.
A 20% wettable powder was prepared by mixing 50 parts by weight of the test compound with 200 parts by weight of the carrier. This wettable powder was dispersed in pure water to obtain a wettable powder dispersion having a predetermined concentration. Separately, rice, Taenia japonicus, and a sialet seed germinated with radish seeds for 20 days were prepared, the above-mentioned wettable powder dispersion was added, and seedlings were grown for 7 days in a constant temperature oven at 25 ° C to observe the degree of growth. The results are displayed as follows: 1 = no effect, 2 = 25% growth inhibition, 3 = 50% growth inhibition, 4 = 75% growth inhibition, 5 = complete death.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Yagihara 煕 Himeji-shi, Hyogo Prefecture Form of town 1177-5 (72) Inventor Yasuo Morishima 3-6 of 11 Tsujigaoka, Tarumi-ku, Kobe, Hyogo Prefecture (72) Inventor Hirobe Kouwa 940 Daisen, Aboshi Ward, Himeji City, Hyogo Prefecture

Claims (8)

[Claims] 1. A formula (I) [In the formula, R is-(CH ₂ ) n-R ₁ (n is an integer of 1 to 3; R ₁ is a lower alkoxy group, a C _{3 to} C ₁₁ alkyl group, a lower alkenyl group, a 5- or 6-membered different Ring group or an aryl group substituted with 1 to 2 substituents of a halogen atom, lower alkyl and lower alkoxy); R ₂ and R ₃ are each a benzene ring;
They are bonded to the 3, 4 or 5 position and are the same or different and each represents a hydrogen atom, a halogen atom, a nitro group, a lower alkyl group, a halogenated lower alkyl group or a lower alkoxy group. ] 1,4-dihydro-2,6-dimethyl-4-oxo- having
3-Pyridinecarboxamide compounds and addition salts thereof. 2. The method according to claim ₁ , wherein the lower alkyl, lower alkenyl or lower alkoxy group in R ₁ , R ₂ and R ₃ in R of the formula (I) has 1 to 5 carbon atoms. Compound. 3. The compound according to claim ₁ , wherein the halogen atom in R ₁ , R ₂ and R ₃ in R of the formula (I) is chlorine, bromine or fluorine atom. 4. The compound according to claim ₁ , wherein the aryl group in R ₁ , R ₂ and R ₃ in R of the formula (I) is a phenyl group. 5. The compound according to claim ₁ , wherein the heterocyclic group in R ₁ in R in formula (I) is a furyl or pyridyl group. 6. A compound of formula (I) Is 3-methylphenyl, or 3 or 4-chlorophenyl. 7. — (CH ₂ ) n—R _{1 of} formula (I) is 4-fluorophenylmethyl, 4-chlorophenylmethyl or 4
-The compound of claim 1 which is methylphenylmethyl. 8. 1- (4-fluorophenylmethyl) -1,
4-dihydro-2,6-dimethyl-4-oxo-N-phenyl-3-pyridinecarboxamide, 1- (4-chlorophenylmethyl) -1,4-dihydro-2,6-dimethyl-4-
Oxo-N-phenyl-3-pyridinecarboxamide,
1- (3-chlorophenylmethyl) -1,4-dihydro-
2,6-Dimethyl-4-oxo-N-phenyl-3-pyridinecarboxamide, 1,4-dihydro-2,6-dimethyl-
1- (3-methylphenylmethyl) -4-oxo-N-
Phenyl-3-pyridinecarboxamide, 1,4-dihydro-2,6-dimethyl-1- (4-methylphenylmethyl) -4-oxo-N-phenyl-3-pyridinecarboxamide, N- (4-chlorophenyl)- 1,4-dihydro-2,6-dimethyl-1- (4-methylphenylmethyl) -4-oxo-3-pyridinecarboxamide, N-
(4-Chlorophenyl) -1- (4-chlorophenylmethyl) -1,4-dihydro-2,6-dimethyl-4-oxo-
3-pyridinecarboxamide, 1- (4-chlorophenylmethyl) -1,4-dihydro-2,6-dimethyl-N- (3
-Methylphenyl) -4-oxo-3-pyridinecarboxamide, 1- (4-chlorophenylmethyl) -1,4-
Dihydro-2,6-dimethyl-N- (4-methylphenyl) -4-oxo-3-pyridinecarboxamide, 1,4
-Dihydro-2,6-dimethyl-N- (3-methylphenyl) -1- (4-methylphenylmethyl) -4-oxo-3-pyridinecarboxamide, N- (3-chlorophenyl) -1- (4- Chlorophenylmethyl) -1,4-dihydro-2,6-dimethyl-4-oxo-3-pyridinecarboxamide, or N- (3-chlorophenyl) -1,4
A compound according to claim 1 which is -dihydro-2,6-dimethyl-1- (4-methylphenylmethyl) -4-oxo-3-pyridinecarboxamide.