JPS589099B2 - Quinazoline - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing quinazoline compounds having anti-inflammatory and analgesic effects.

Specifically, general formula (I) (wherein, R1 is a hydrogen atom or a halogen atom, R2 is a phenyl group, or a phenyl group substituted with a halogen atom or a trifluoromethyl group, and R3 is a hydrogen atom or a lower alkyl group) A compound represented by the general formula (I) (wherein R4 represents a lower alkyl group, A represents an alkylene residue, and X represents a hydroxyl group, an alkoxy group, or an acyloxy group) in the presence of an alkali metal compound. This invention relates to a method for producing a quinazoline compound represented by the general formula (I) (wherein R1, R2, A and X have the same meanings as above) by reacting the compound represented by

As a method for producing the object compound of the present invention, ■ a method in which the hydrogen atom at the 3-position of the -substituted quinazoline-2.4 (IH.3H) monodione is substituted with a hydroxyalkyl group, an alkoxyalkyl group, an acyloxyalkyl group, etc. is generally known, but this method has problems in terms of raw materials and cost.
In addition, the manufacturing process is long, and when commercialized, there are various problems, so it is not always satisfactory.

The present invention has improved these points, and according to the present invention, a highly pure target compound can be easily produced in one step.

Furthermore, to describe the usefulness of the present invention, it is economically very useful because it requires less raw material than conventional methods and the reaction proceeds at low temperature and in a short time.

Furthermore, there is no generation of bad odor associated with the reaction at low temperatures, making it a very preferable method in terms of work hygiene.

A more detailed explanation of the present invention will be given below.

Examples of the compound represented by the general formula (I) include 2-anilinobenzoic acid, 2-(o-chloroanilino)benzoic acid, 2-
(m-promoanilino)benzoic acid, 2-(m-}lifluoromethylanilino)benzoic acid, 2-(m-methylanilino)benzoic acid, 2-(m-methoxyanilino)benzoic acid, 4-chloro2- Anilinobenzoic acid, 4-chloro2-(m-chloroanilino)benzoic acid, 2-(pendylamino)benzoic acid, 2-(p-methylanilino)benzoic acid, 2-(p-chloroanilino)benzoic acid, or esters thereof is appropriate.

Further, as a compound represented by general formula (I), N-(2-
hydroxyethyl)carbamate, N-ethoxymethylcarbamate, N-(2-ethoxyethyl)carbamate, N-penzylcarbamate, N-phenethylcarbamate, N
-(2-acetoxyethyl)carbamate and the like are suitable.

The compound represented by the general formula (I) and the compound represented by the general formula (I) are reacted at a ratio of about 1:10.

Furthermore, an alkali metal compound such as sodium ethylate, sodium hydroxide, or sodium amide is used, and the reaction is
This can be achieved by keeping it at 0 to 60°C for several hours (about 3 hours).

According to the present invention, the quinazoline compound represented by the general formula (I) can be produced easily and with high yield.

The present invention will be specifically explained below using Examples.

Example 1 2-(m-trifluoromethylanilino)benzoic acid5.
91 with 20 ml of diethylene glycol dimethyl ether
After dissolving 0.5 g of sodium metal in 20 ml of ethanol, a solution prepared by dissolving 0.5 g of sodium metal in 20 ml of ethanol was added dropwise.

Next, a solution of 2.7 g of ethyl N-(2-hydroxyethyl)carbamate dissolved in diethylene glycol 1011K was added dropwise at 30°C, and the mixture was heated at 40°C for 2 hours and then at 60°C.
After the reaction was completed by keeping it warm for 1 hour, insoluble materials were separated and the solvent was recovered from the solution.

The obtained viscous residue was adsorbed on a column packed with 500 g of silica gel and eluted with a benzene-ethyl acetate mixed solvent to obtain ■-(m-trifluoromethylphenyl)-3-
(2-hydroxyethyl)quinazoline-2.4(1H.
3.4 g of 3H)-dione were obtained.

The melting point of this material was 139-140°C.

Example 2 After dissolving 5.21 methyl 2-(m-chloroanilino)benzoate in 20 ml of diethylene glycol dimethyl ether, 0.5 P of metallic sodium was dissolved in 20 ml of ethanol.
1 of the solution was added dropwise.

Next, a solution of 2.9P of ethyl N-(2-ethoxyethyl)carbamate dissolved in 10 ml of diethylene glycol was added dropwise at 30°C, and the reaction was completed by keeping at 40°C for 2 hours and at 60°C for 1 hour. After that, insoluble materials were separated and the solvent was recovered from the slurry.

The resulting viscous residue was eluted with a benzene-ethyl acetate mixed solvent adsorbed on a column packed with 500 g of silica gel to obtain ■-(m-chlorophenylene/)-3-(2-ethoxyethyl)quinazoline- 3.51 of 2.4(IH.3H)-dione was obtained.

The melting point of this material was 115-116°C.

Examples 3 to 18 According to the method of Examples 1 to 2, the compounds shown in the following table were obtained in good yields.

Claims (1)

[Scope of Claims] 1 General formula (I) (wherein, R1 is a hydrogen atom or a halogen atom, R2 is a phenyl group, or a phenyl group substituted with a halogen atom or a trifluoromethyl group, and R3 is a hydrogen atom or a phenyl group substituted with a trifluoromethyl group). (representing a lower alkyl group) in the presence of an alkali metal compound, a compound represented by the general formula (I) (wherein R4 represents a lower alkyl group, A represents an alkylene residue, and X represents a hydroxy group, an alkoxy group, or A method for producing a quinazoline compound represented by the general formula (I) (wherein R1, R2, A and X have the same meanings as above), characterized by reacting the compound with a compound represented by the formula (representing an acyloxy group) .