非布索坦的合成

对羟基苄腈与硫代乙酰胺反应得到4-羟基硫代苯甲酰胺,与2-氯乙酰乙酸乙酯环合后与六亚甲基四胺进行Duff反应得到2-(3-甲酰基-4-羟基苯基)-4-甲基-5-噻唑甲酸乙酯,再相继与盐酸羟胺/甲醇钠反应、异丁基溴成醚后碱性水解,制得抗痛风药非布索坦,总收率为28%.

Synthesis of Febuxostat

Febuxostat,an antipodagrics,was synthesized from 4-hydroxybenzonitrile by reaction with thioacetamide to give 4-hydroxythiobenzamide,which was subjected to cyclization with 2-chloroethyl acetoacetate,Duff reaction with urotropine to afford ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylate,followed by reaction with hydroxylamine hydrochloride,etherifi cation and then hydrolysis with an overall yield of 28%.