JPS582947B2 - Sinquinapyridopyrimidinedione - Google Patents

Description

Detailed Description of the Invention The present invention is based on the general formula (I) (wherein A is a linear or branched alkylene group having 2 to 3 carbon atoms, and R is a phenyl group, a halogen atom, or a lower alkyl group). , a phenyl group substituted with a lower alkoxy group, a nitro group, a trifluoromethyl group, a cycloalkyl group, a benzyl group, or a benzyl group substituted with a halogen atom). It is related to.

More specifically, the compound represented by the general formula (II) (wherein A and R have the same meanings as above, X represents an oxygen atom, and B represents a vinyl group and a tetrahydropyranyl group) has the general formula COY2 The present invention relates to a method for producing a compound represented by the general formula (I) by reacting a compound represented by (III) (wherein Y represents a halogen atom).

To explain R in the general formulas (I) and (II) in more detail, R is a phenyl group, or chlorine, bromine, fluorine,
A halogen atom such as iodine, a lower alkyl group such as methyl or ethyl, a lower alkoxy group such as methoxy or ethoxy, a nitro group or a trifluoromethyl group, etc. can be present at any position of 1 to 2
Represents a substituted phenyl group.

In addition, cycloalkyl groups include cyclohexyl groups and lower alkyl-substituted cyclohexyl groups, benzyl groups, or chlorine,
Represents a benzyl group substituted with a halogen atom such as bromine, fluorine, or iodine.

The compound of general formula (II) which is the starting material of the present invention is 2
-Amine It can be obtained in good yield by reacting amines corresponding to nicotinic acid chloride derivatives.

The reaction formula of the present invention is as follows.

In carrying out the invention, tetrahydrofuran, diglyme,
In an inert solvent such as benzene, toluene, carbon tetrachloride, dimethylformamide, etc., in the presence of a metal compound such as sodium hydride, sodium amide, sodium ethylate, a compound represented by general formula (III) is added dropwise under water cooling, and the mixture is heated to room temperature. The reaction is completed by stirring for 1 to 2 hours.

A pure product can be obtained from the reaction product by distilling off the solvent under reduced pressure and recrystallizing the residue from an organic solvent such as methanol, or by separating and purifying it using column chromatography.

The compound obtained by the method of the present invention is a new compound that has not been described in any literature, has pharmacological effects such as analgesic action, anti-inflammatory action, and central nervous system depressing action, and is an industrially useful compound as a pharmaceutical.

The present invention will be further explained with reference to Examples below.

Example 1 2-(m-trifluoromethylanilino)-N-(2-
After dissolving 3.5 g of (vinyloxyethyl)nicotinamide in 30 ml of tetrahydrofuran, 1.0 g of about 50% sodium hydride was added and stirred for 30 minutes.

Next, 10 g of a 40% phosgene-carbon tetrachloride solution was added dropwise under water cooling, and the mixture was stirred at room temperature for 2 hours.

Then, after decomposing excess phosgene with water, the solvent was distilled off under reduced pressure, and the residue was dissolved in ethyl acetate and adsorbed on a column packed with alumina, developed with ethyl acetate, the solvent of the eluate was distilled off, and the residue was dissolved. Recrystallization from ether gives colorless prismatic crystals of 1-(m-trifluoromethylphenyl)-3-(2-
1.9 g of hydroxyethyl)pyrido[2,3-d)pyrimidine-2,4(1H,3H)-dione was obtained.

The melting point and elemental analysis values of this substance were as follows.

Melting point 160-162℃ Elemental analysis value C16H12F3N3O3 Theoretical value C: 54.70 H: 3.44 N: 11.96
Actual value C: 54.67 H: 3.38 N: 12.05
Example 2 3.8 g of 2-(m-chloroanilino)-N-[2-(2-tetrahydropyranoxy)ethyl]nicotinamide
After dissolving in 30 ml of tetrahydrofuran, 1.0 g of about 50% sodium hydride was added and stirred at room temperature for 30 minutes.

Next, 10 g of a 40% phosgene-carbon tetrachloride solution was added dropwise under water cooling, and the mixture was stirred at room temperature for 2 hours.

Then, after decomposing excess phosgene with water, the solvent was distilled off under reduced pressure, and the residue was dissolved in ethyl acetate and adsorbed on a column packed with alumina, developed with ethyl acetate, the solvent of the eluate was distilled off, and the residue was dissolved. Recrystallization from methanol gave colorless prismatic crystals of 1-(m-chlorophenyl)-3-(2-hydroxyethyl)pyrido(2,3-d)pyrimidine-2,4(
1.3 g of 1H,3H)-dione was obtained.

The melting point and elemental analysis values of this substance were as follows.

Melting point 176-177℃ Elemental analysis value C15H12ClN3O3 Theoretical value C: 56.70 H: 3.81 N: 13.23
Actual value C: 56.82 H: 3.88 N: 13.19
Examples 3-35 According to the method of Examples 1-2, the compounds shown in the following table were obtained in good yields.

Claims (1)

[Scope of Claims] 1 General formula (wherein A is a linear or branched alkylene group having 2 to 3 carbon atoms, X is an oxygen atom, B is a vinyl group or a tetrahydropyranyl group, R represents a phenyl group, a phenyl group substituted with a halogen atom, a lower alkyl group, a lower alkoxy group, a ditro group, a trifluoromethyl group, a cycloalkyl group, a benzyl group, or a benzyl group substituted with a halogen atom). Represented by the general formula COY2 (wherein A and R have the same meanings as above) characterized by reacting a compound represented by the general formula COY2 (wherein, Y represents a halogen atom) with the compound represented by A method for producing a novel pyridopyrimidinedione derivative.