JPS5811866B2 - Quinazoline Dione - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides compounds of the general formula (I) (wherein R1 is a hydrogen atom or a halogen atom, and R2 is a phenyl group, or a halogen atom, a lower alkyl group, a lower alkoxy Novel production of quinazolinedione derivatives represented by a phenyl group or benzyl group substituted with 1 or 2 trifluoromethyl groups, R3 means a lower alkyl group substituted with a hydroxyl group, an alkoxy group or an acyloxy group) It is about law.

More specifically, the compound represented by the general formula (■) (wherein M is a hydrogen atom or a lower alkyl group, and R1 and R2 have the same meanings as above) is given the general formula R3NHCONHR4 (■) (wherein, R3 has the same meaning as above, and R4 has the same meaning as hydrogen atom or R3. .

To explain R2 in the general formulas (1), (II) and (■) in more detail, R2 is a phenyl group, a halogen atom such as chlorine, bromine, or fluorine, a lower alkyl group such as methyl or ethyl, methoxy, 1 to 2 lower alkoxy groups such as ethoxy or trifluoromethyl groups at any position
Represents a substituted phenyl group or a benzyl group.

Conventionally, methods for producing quinazoline-2,4(1H,3H)-dione derivatives include 1-monosubstituted quinacillin-2,
A method is known in which the hydrogen atom at the 3-position of a 4-(1H,3H)-dione derivative is substituted with a hydroxyalkyl group, an alkoxyalkyl group, an acyloxyalkyl group, etc., but this method is limited by raw materials, cost, manufacturing process, The purity and yield of the target compound are not necessarily satisfactory.

The present invention improves these points, and according to the present invention, a highly pure target compound can be easily produced.

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

Examples of the compound represented by general formula (II) include 2
-anilinobenzoic acid, 2-(p-chloroanilino)benzoic acid, 2-(m-chloroanilino)benzoic acid.

Froic acid, 2-(m-bromoanilino)benzoic acid, 2-(m
-methylanilino)benzoic acid, 2-(m~fluoroanilino)benzoic acid, 2-(m-)lifluoromethylanilino)benzoic acid, 4-chloro-2-anilinobenzoic acid, 4
-Chloro-2-(m-chloroanilino)benzoic acid, 4-
Chloro-2-(m-trifluoromethylanilino)benzoic acid, 2-benzylaminobenzoic acid, 2-(p-tolylmethyl)aminebenzoic acid, 2-(p-chlorophenylmethyl)aminebenzoic acid and esters thereof Appropriate.

In addition, as a compound represented by the general formula (■), N-(
2-hydroxyethyl)urea, N-ethoxymethylurea, N-(2-ethoxyethyl)urea and N,N-di(
2-hydroxyethyl) urea and the like are suitable.

In order to carry out the present invention, the compound represented by the general formula (lI) and the compound represented by the general formula (■) must be mixed at 100 to 15
It can be produced in good yield by reacting at 0°C for 3 to 4 hours.

The present invention will be specifically explained below using Examples.

Example 1 Methyl 2-(m-trifluoromethylanilino)benzoate 10. F is N-(2-hydroxyethyl)urea 12
After stirring on an oil bath at 150°C for 3 hours, the reaction solution was dissolved in a mixed solvent of benzene and ethyl acetate, and adsorbed on a column packed with silica gel to dissolve a mixed solvent of benzene and ethyl acetate ( The solvent was distilled off from the eluate and the residue was recrystallized from methanol and ether to give colorless prismatic crystals of 1-(m-trifluoromethylphenyl)-3-(2- hydroxyethyl)
6.5 g of quinazoline-2,4(1H,3H)-dione was obtained.

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

Example 2 13 g of N-(2-ethoxyethyl)urea was added to 5.2 g of methyl 2-(m-chloroanilino)benzoate, and the mixture was heated on an oil bath.
After stirring at 50°C for 4 hours, the reaction solution was dissolved in a mixed solvent of benzene and ethyl acetate, and adsorbed on a column packed with silica gel.
The solvent was distilled off from the eluate, and the residue was recrystallized from ethanol to obtain colorless prism crystals of 1-(m
3.6 g of -chlorophenyl)-3-(2-ethoxyethyl)quinazoline-2,4(IH,3H)-dione was obtained.

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

Examples 3-20 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 R1 is a hydrogen atom or a halogen atom, R2 is a phenyl group, or substituted with 1 to 2 halogen atoms, lower alkyl groups, lower alkoxy groups, or trifluoromethyl groups) a phenyl group or a benzyl group, M means a hydrogen atom or a lower alkyl group) and a compound represented by the general formula % (wherein R3 is a lower alkyl group substituted with a hydroxyl group, an alkoxy group, or an acyloxy group) , R4 has the same meaning as hydrogen atom or R3) and 10
A method for producing a quinazolinedione derivative represented by the general formula (wherein R1, R2 and R3 have the same meanings as above), which comprises reacting at 0 to 150°C for 3 to 4 hours.