Synthesis of isothiazolopyrimidine derivatives as potential anti-inflammatory agents

Abstract

This investigation was to study the synthesis method of 5-substituted-3-(substitutes) amino-6-hydroxy [or (substituted) amino] isothiazolo [3,4-d] pyrimidine-4-one which were expected to possess anti-inflammatory activity. The target products were synthesized via 4 steps, ie: 1) synthesis of isothiazole ring by the reaction of ethylcyanoacetate, sodium ethoxide and methyl or phenylisothiocyanate, then cyclisation with cold chloramines solution. 2) Synthesis of isothiazolo [3,4-d] pyrimidine derivatives by the reaction of isothiazole with methyl or phenylisothiocyanate under reflux condition. 3) Methylation of isothiazolo [3,4-d] pyrimidine derivatives with dimethyl sulphate under alkali condition to afford four 5-substituted-6-methylthio-3-(substituted) aminoisothiazolo [3,4-d] pyrimidine-4-ones and three 7-methyl-5-substituted-3-(substituted) aminoisothiazolo [3,4-d] pyrimidine-4-one-6-thiones. 4) Hydrolysis of methylsulphide intermediates with 6N hydrochloric acid under reflux condition to obtain four 5-substituted-3-(substituted) amino-6-hydroxyisothiazolo [3,4-d] pyrimidine-4-ones. When treating 5-methyl-6-methylthio-3-methylamino-isothiazolo [3,4-d] pyrimidine-4-one with piperidine, the expected 5-methyl-3-methylamino-6-(1’-piperidino) isothiazolo [3,4-d] pyrimidine-4-one was obtained.