SU1097620A1 - Process for preparing diethyl-n-(6-methyl-pyridyl)-2-aminomethyl malonate - Google Patents

Abstract

METHOD FOR OBTAINING DOETHYL-K-

Description

The invention relates to an improved method for producing diethyl-N-(6-methylpyridyl-2)aminomethylmalonate, which is a semi-product of the synthesis of medicinal substances, for example nevigramon ClJ.

The closest to the proposed method in terms of technical essence and the achieved result is a method for obtaining diethyl-N-(6-methylpyridyl-2-)aminomethylenemalonate, characterized by the fact that N-(6-methylpyridyl-2-)n,N-dimethylformamidine is treated with malonic ether in a molar ratio of 1:1-1:3 at 100-150 C, preferably at , followed by isolation of the target product in pure form (content of the main substance 94-95%) by treatment with hydrochloric acid 2.

However, this method requires prolonged (12-13 h) heating of the starting reagents at 130 °C and a significant (threefold) amount of malonic ester to achieve the maximum yield of the target product (48-51%). By reacting equimolecular amounts of the starting reagents (N-(6-methylthiridyl-2)-N,N-dimethylformamidine and malonic ester) at 130 °C for 12 h, the target product can be obtained with a yield of 36% of the theoretical yield.

The aim of the invention is to accelerate the process of obtaining diethyl-N-(6-methylpyridyl-2-)-aminomethylenemalonate and to increase the yield of the target product.

The stated objective is achieved according to the method of creeping diethyl N-(6-methylpyridyl-2-)aminomethylenemalonate, which consists in the fact that equimolecular amounts of N-(6-methylpyridyl-2-)-N 5N-dimethylformamidine and malonic ester are heated in an acetic acid medium at 130-150 C, the reaction is carried out for 45-60 min, the target product is separated after cooling the reaction mass to

A distinctive feature of the method is that the reaction is carried out in the presence of acetic acid.

Example 1. 80 ml (0.48 mol) of N-(6-methylpyridyl-2-)-N,N-dimethylformamidine, 75 ml (0.48 mol) of malonic ester and 80 ml of acetic acid are heated under reflux at 140-145 ° C for 50 min, cooled to 20-25 C and left at this

temperature overnight. The crystallized reaction mass is suspended in 1 liter of water, the light yellow crystals are filtered, washed with 3x100 MP of water and dried in air. 66.1 g of diethyl N- (6-methylpyridyl-2-) aminomethylenemalonate with a content of the main substance of 95.3% are obtained.

Yield 47.15%. M.p. 96-97 C.

Found, %: C 60.32; H 6.22; N 9,S2 C,,0

Calculated, %: C 60.42} N 6.52, N 10.07.

Example 2. 8 ml (0.048 mol); N-(6-methylpyridyl-2)-N,N-dimethylformamidine, 7.5 ml (0.048 ml) malonic ester and 6 ml acetic acid are heated under reflux at 135-140 C for 45 min, cooled to room temperature, suspended in 200 MP water, the precipitate is filtered off, washed on a filter with 3x25 ml of water, and dried in air. 6.8 g of ethyl N-(6-methylpyridyl-2)-aminomethylenemalonate are obtained with an active substance content of 96.6%.

Yield 49.17%. M.p. 98-99 C.

Example 3. 85 ml (0.51 mol) of N-(6-methylpyridyl)-dimethylformamidine, 78 ml (0.5 mol) of malonic ester and 40 ml of acetic acid are heated under reflux at 150 C for 55 min, cooled to room temperature, suspended in 800 ml of water, the precipitate is filtered off, washed on a filter with 3x100 ml of water and dried in air. 69.8 g of diethyl-N-(6-methylpyridin-2)-aminomethyl ester with a content of the main substance of 96.3% are obtained.

Yield 48.3%. M.p. 98-99° C.

A mixture of 4.4.8 ml (0.0288 mol) of N-(6-methylpyridyl-2)-N,N-dimethylformamidine, 3.9 ml (0.025 mol) of malonic ester and 2 ml of acetic acid are heated under reflux at 14 °C to 145 °C for 60 min, cooled to room temperature and left in the refrigerator overnight. The crystallized reaction mass is suspended in 100 MP of cold water, the light yellow crystals are filtered off, washed with 3x15 ml of cold water and dried in air. 3.9 g of diethyl N-(6-methylpyridyl-2)-aminomethylenemalonate are obtained with an active substance content of 94.5%.

3 . 10976204

Yield 53%. M.p. 96-97 s.15 h to 45-60 min) and provides the desired product of good quality.

ethyl-N-(6-methylpyridyl-2)-aminomethyl-quality (containing the main

lenmalonate is technically simple, allowing the substance to be produced (94-96%) without additional

let's reduce the consumption of sf, reduce5 cleaning with a yield of 47-53% of the theoretical duration of the process (from 12-year.

Claims (1)

A METHOD FOR PRODUCING DIETHYL-N-(6-METHYLPYRIDYL-2-)AMINOMETHYLENE MALONATE by reacting equimolecular amounts of ^(6-methylpyridyl-3-)-^,^-dimethylformamidine and malonic ester at a temperature of 130-150 °C, characterized in that, in order to accelerate the process and increase the yield of the target product, the reaction is carried out in an acetic acid medium. |s L e e> <