SU328089A1 - - Google Patents

Description

METHOD OF OBTAINING

The invention relates to the production of heterocyclic sutures, compounds combining pyrimidine and thiazepine rings, which can be used in pharmaceutical industry.

Condensed benzthiazepinones are known, obtained, for example, by Beckmann rearrangement of the thiochromone oxime.

Also known is the process for the preparation of pyrilschdo-4, 5-L 1,4-thiazines by reacting 5-amino-6-mercaptoirimidine with a-halogencarbamide acid or its lower alkyl ester. Products are isolated by known methods.

An attempt to carry out a similar reaction for obtaining nirnmidothiasenins did not lead to a failure. The formation of the thiazepine cycle, both in the alcoholic alkali environment and in the presence of acidic agents, did not occur. It took the replacement of one of the starting materials (a-halo: gencarboxylic acid or its ester), used in the synthesis of pyrmidothiazines, with more than 1-reactive, b “initial compound — halogen-nhydride a-halogenocarboxylic acid, i.e. the proposed method can not be considered obvious.

f o

Ls

where R is lower alkyl, lower al.coxyl,

halogen atom.

The method consists in the fact that the corresponding 5-amino-6-mer-1-Topopirpmidine derivative is reacted with p-halo-nroniopic acid halide.

in the medium | solvent, narnn.mer acetone, acetonitrile, in the presence of an acid acceptor. As the acid acceptor, it is desirable to use alkali carbonate (metal. The process is preferably carried out at 70-

90 ° C. Products are isolated in a known manner.

In this reaction, 5- (| 3-halogen.ronionyl) amino-b-mercantopyrimidine is formed as an intermediate product, which cyclizes when heated to the desired product. The latter is isolated by absorption with an organic solvent. Pyrimido-4,5-b 1,5-thiazepinones Example 1. Preparation of 4-methoxypyri; mido-4, 5- & 1,5-tiazepione-6. A mixture of 1 g (6.3 mmol 4-methoxy-5-amino-6mercaptapyrimidine, 0.9 g (6.5 mmol} K2CO3 and 1.3 g (6.8 mmol} chloro-hydrochloride mlropionic acid in 100 ml of anhydrous acetone is stirred for 6 hours at 18–20 ° C. The precipitate which has separated out is filtered off and extracted with boiling acetonitrile (50X2). Extraction: ct is evaporated, the residue is triturated with water and filtered, to obtain 0.9 g (70%) of product with m.pl. 160-162 C (ethanol). Found,%; C 45.75; H 4.21; N 19.95; S 15.02. You are 1%,%: C 45.48; H 4.29; N19, 89; S 15.18. Example 2. Preparation of 4-methyl mercapto-pyrimido-4, 5 - 1,5 1,5-thiazepino1 on 6. To a suspension of 1 g (5.8 mmol } 4-.methyl1, mercapto-5-amino-6-mer1cap0 | iirimidine and 1.6 g (11.6 mmol) of K2CO3 in 1.2 ml of anhydrous acetone were added 1.2 g (585 mmol} of acid chloride | 3-bromo-1-ProPionic acid the mixture is stirred at 18–20 ° C for 5 h, filtered, the filter cake is extracted with boiling acetonitrile, the extract is evaporated and 0.9 g (68.5%) of product is obtained, mp 200–202 ° C ( from ethanol). Paydeno,%: C 42.1; H 4.01; N 18.4; S 27.94. Calculated,%: C 42.27; P 3.99; N 18.5; S 28.21. The subject of the invention 1. A method of producing pyrimido-4,5- & 1.5 thiazbpinones of the general formula where R is lower alkyl, lower alkoxy, halogen atom, characterized in that the corresponding 5-amino-6-mercaptonirimidine derivative is reacted with p-halopronionic acid halide in a solvent, for example acetone, acetonitrile, in the presence of acid acceptor, followed by isolation of products in a known manner. 2. A method according to Claim 1, characterized in that the process is carried out at 70-90 ° C. 3. A method according to claim. 1 and 2, characterized in that an alkali metal carbonate is used as an acid acceptor.