SU232268A1 - METHOD OF OBTAINING 6-ALKYLPYRIMIDO- - Google Patents

Description

The invention relates to the field of producing compounds that can be used in organic synthesis, with the aim of obtaining on their basis physiologically active substances.

The proposed method for the preparation of 6-alkylpyrimido- (4,5-b) - (1,4) -thiazinyl-7- or 6-alkylpyrazino- (2,3-b) - (1,4) -thiazinyl-7-carboxylic acids lies in the fact that 5-amino-6-mercaptopirimidines or 2-1 mercapto-3-aminopyrazines are treated with a-chloroacetoacetic ester in alcohol in the presence of an equimolecular amount of alkali, followed by isolation of the target product in a known manner, for example by distilling the alcohol, treating the residue with water and filtering.

Example 1. 2-amino-4,6-dimethyl-5H ethyl ester - pyrimido- (4,5-b) - (1,4) -thiazinyl-7-carboxylic acid.

To a solution of 2 5 (0,0122 mol) of a-chloroacetoacetic ester in 10 ml of ethanol at 18-20 ° C is added gradually a solution of 1 g (0,0064 mol) of 2,5-diamino-4-methyl-6-mercaptopyrimidine in 20 ml of ethanol containing 0.48 g (0.0084 mol) of potassium hydroxide. The reaction mixture was stirred at 40 ° C for 3 hours, the solvent was distilled off in vacuo to dryness, the residue was treated with water and filtered. Obtain 1.1 g (65%) of product with so pl. 175-177 ° (with decomp.). It is light orange

fine-crystalline powder with m. pl. 175 - 177 ° C (with decomp. Of ethanol).

IR spectrum: 1640 c. (CO - ester), 3200, 3320, 3460 cu-i (NH, KP-,). Paydeno,%: C 49.30; H 5.34; N 21.17; S 12.33.

With nHuNUGoS.

Calculated,%: C 49.60; P 5.30; N 21.04; S 12.04.

Example 2: 4-methoxy-6-methyl-5H-pyrimido- (4,5-b) - (1,4) - tnazinyl-7-carboxylic acid ethyl ester.

To a solution of 1.1 g (0.007 mol) of 4-methoxn-5-amino-6-mercaptopyrimidium in 20 nl of ethanol containing 0.52 g (0.0093 mol) of potassium hydroxide at -5 ° C is added 1.4 s (0 , 0085.h (o.yy) a-chloroacetoacetic ester in 10 ml of ethanol.

The reaction mass is stirred at the same temperature for 2 hours, the precipitate is filtered off with KCl and the filtrate is evaporated in vacuo. The residue is dissolved in 20 ml of chloroform, passed through a column of AljO :; and the chloroform eluates evaporated. Obtain 1.8 g (96%) of the product with so pl. 134-136 ° C. This is a bright orange crystalline powder with mp. 141 - 143 ° С (from cyclohexane). 3 H 5.10; N 15.91; C, 49.74; Found, S 11.90. CnHisNsOgS. 4.90; N 15.72; : C 49.42; H Calculated, S 12,0. Example 3. 2,3,7-Trialkylpyrazino- (2,3-b) - (1,4) -thiazinyl - 7 - carboxylic acid ethyl ester. To 0.5 g (0.0039 mol} of 2-mercapto-3-amino5, 6-dimethylpyrazium in (ml of methanol containing 0.22 g of KOH (0.0039 mol}), a methanol solution of 0.64 is added dropwise g (0.0039 mol of sb-chloroacetoacetic ester and stirred for 24 hours at room temperature until neutral. Then the alcohol is distilled off in a vacuum, the residue is triturated with water and a few drops of snort, the solid is filtered and dried. A yield of 0.93 g is obtained ( 89.6% of the product with mp 131–133 ° C. These are yellow crystals with mp 146–147 ° C (from mixed water: ethanol 1: 1). IR spectrum: 1678 cm ( CO - ester), 3340 slg-1 (NH). Found,%: C 54.20; H 5.55; N 15.66; S 11.80. CiaHisNgSOa. Calculated,% C 54.32; H 5.69; N 15.84; S 12.08. of the invention. The method of producing 6-alkyl pyrimido- (4,5-b) (, 4) -tnasinyl-7- or 6-alkylpyrazino- (2,3-b) (1,4) -thiazinyl-7-carboxylic acids, characterized by that 5-amino-6-mercapto-nirimidines or 2-mercapto-3-aminopyrazines are treated with a-chloroacetoacetic ester in alcohol in the presence of an equimolar amount of alkali, followed by isolation of the target product in a known manner.