非布索坦的合成  

Synthesis of Febuxostat

作　　者：郑凡[1] 钱珊[1] 杨莉[1] 吴勇[1] 

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《中国医药工业杂志》2009年第10期726-728,共3页Chinese Journal of Pharmaceuticals

摘　　要：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%。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, etherification and then hydrolysis with an overall yield of 28 %.

关 键 词：非布索坦 抗痛风药 高尿酸血症 合成 

分 类 号：R979.9[医药卫生—药品]