CS249493B1 - Method for the Preparation of 3- [2- (2-Banzimidazolyl) -benzoyloxyethyl] -4 (3H) -quinazolinone - Google Patents

Abstract

The invention relates to a method for the production of 3-(2-(2-benzimidazolyl-benzoyloxyethyl)-4(3H)-oquinazolinone, a non-toxic, effective analgesic. The substance is prepared by converting 2-(2-benzimidazolyl)benzoic acid with sodium ethylate in dimethylformamide to the sodium salt, which reacts, without being isolated, in the same reaction medium with 3-(2-iodoethyl)-4(3H)-quinazolinone. The product is isolated by pouring the reaction mixture into water and purified by crystallization.

Description

The present invention relates to a process for the preparation of 3- (2- (2-benziaidezolyl) bensoyloxyethyl) -4 (3H) -quinazolone of the formula 1

(AND)

This ee has hitherto been obtained by first preparing 2- (2-benzimldazolyl) benzoic acid with 1,1'-carbonyldiiaidazole with the corresponding imidazolide which was reacted without isolation with 3- (2-hydroxyethyl) -4 (3H). 1-quinazolinone (Serial Certificate No. 247557 PV 2662-84) The disadvantage of this embodiment is the use of the difficult to obtain expensive 1,1'-carbonyldiiaidazole and high demands on its purity,

These disadvantages have been overcome by the development of a process for the preparation of 3- [2- (2-benzimidazolyl) benzoyloxyethyl] -4 (3H) -quinazolinone of the formula I according to the invention, which comprises the preparation of 2- (2-benzimidazolyl) benzoic acid. II

COOH is first converted to an alkali metal salt, for example sodium, which is reacted with 3- (2-iodoethyl) -4 (3H) -quininasolnon of formula II

in an inert organic solvent of the C 1 -C 4 alkanol type, C 1 -C 2 alkanecarboxylic acid amide or alkyl amide or a mixture thereof, at a temperature of from 30 ° C to the boiling point of the reaction mixture.

The compounds of formulas II and III serving as starting materials in the process of the invention are readily accessible by methods described in the literature (DW Hein et al., J. Amer. Chem. Soc. 79, 427, 1957, BS Baker et al., J. Org. Chem., 19, 46, 1952).

In the process according to the invention, it is expedient to prepare a sodium salt from the acid of formula II by treatment with a solution of sodium ethylate in a suitable solvent, preferably dimethylformamide, which is subsequently reacted with the iodoethyl derivative of formula III added in solid form, preferably at a temperature of about 100 ° C. The reaction proceeds well and is generally complete after 2 to 3 hours. The product is isolated by pouring the reaction mixture into water and purifying and crystallizing from 2-propanol.

As mentioned above, the reaction proceeds in other inert solvents, such as acetonitrile, dimethyl sulfoxide, etc., in addition to the solvent of choice, dimethylformamide. Also, the reaction temperature ae can be varied within a relatively wide range without substantially affecting the reaction.

The process of the invention is readily practicable under operating conditions and provides the desired compound of formula I in satisfactory yields.

DETAILED DESCRIPTION OF THE INVENTION The invention is illustrated by the following non-limiting examples.

Example

Sodium ethylate is prepared from 2.4 g of sodium and 200 ml of ethanol, which, after distilling off the ethanol to dryness under reduced pressure in 50 ml of dimethylformamide, is added to a suspension of 23.8 g of 2- (2-benzimidazolyl) benzoic acid in 300 µl of dimethylformamide and 30 g of 3- (2-iodoethyl) -4 (3H) -quinazolinone are added to the solution of the sodium acid salt in dimethylformamide thus prepared. The skiase is heated to 100 ° C and maintained at this temperature with stirring for 2 hours. After cooling to 20-25 ° C, it is left the next day and poured into a large excess of water. The solid is filtered off with suction, washed with water and recrystallized from 2-propopanol. 25 g (62 of the desired ester) are obtained.

Claims (1)

A process for the preparation of 3- [2- (2-benzimidazolyl) benzoyloxyethyl] -4 (3H) -quinazolinone of formula (I): The process of claim 2, wherein 2- (2-benzimidazolyl) benzoic acid of formula 11 (II) Η The COOH is first converted to an alkali metal salt, for example sodium, which is reacted with 3- (2-iodoethyl) -4 (3H) -quinazolinone of formula III nch ₂ CH ₂ (III) in a medium. an inert organic solvent of the C 1 -C 4 alkanol type, the C 1 -C 2 alkanecarboxylic acid amide or alkyl amide, or the melts thereof, at a temperature of from 30 ° C to the boiling point of the reaction mixture.