PROCESS FOR SYNTHESIS 4-HYDROXY-2H-1,2-BENZOTHIAZINE-3-CARBOXAMIDES

摘要

Suggested invention is related to the field of organic chemistry technology, specifically to the process for preparation of the compound 4-hydroxy - 2 - methyl - 2 H - 1 , 2 - benzothiazine - 3 - carboxamide - 1 , 1 -dioxide, of general formula (I), wherein R denotes one of the following radicals: alkyl group (C2-C6), cycloalkyl, benzyl, phenyl, pyridyl, methyl-pyridyl, pyrimidyl, thiazole, isothiazole. Concerning clinical practice, the special interest, as non-steroidal antirheumatics characterized by anti-inflammatory and analgesic properties, belongs to: piroxicam (4-hydroxy-2-methyl-N-(2-pyridinyl-2H-1,2-benzothiazine-3-carboxamid-1,1-dioxide)), isoxicam (4-hydroxy-2-methyl-N-(5-methyl-3-isoxazolyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide)) and sudoxicam (4-hydroxy-2-methyl-N-2-thiazolyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide). Individual characteristics of the present invention are: the use of ethylester and dimethyl formamide with sodium ethoxide for opening of the cycle and for work at low temperatures in the mentioned phase; afterwards, methylation and final condensation with an amine of general formula NH2-Retard tablete, wherein R denotes: 2-pyridyl, alkyl substituted 2-pyridyl, 2-thiazole, 2-thiazole substituted with one or two alkyl groups, while each alkyl has from 1 to 4 carbon atoms or 5-methyl-3- isoxazolyl, using specific catalysts and adsorbents in an inert solvent and inert atmosphere.