2-氨基-N-(2-氯-6-甲基苯基)噻唑-5-甲酰胺的合成  

Synthesis of 2-Amino-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide

作　　者：刘长春[1] 王天扬[1] 张雨晴[1] 

机构地区：[1]江苏食品药品职业技术学院药学院,江苏淮安223003

出　　处：《中国医药工业杂志》2016年第7期848-850,共3页Chinese Journal of Pharmaceuticals

摘　　要：以1,1,3,3-四甲氧基丙烷为原料,经溴化铜溴代后,与硫脲缩合环化合成2-氨基噻唑-5-甲醛,再与2-氯-6-甲基苯胺在溴化亚铜和叔丁基过氧化氢(t-Bu OOH)作用下直接发生氧化酰胺化反应得到抗肿瘤药达沙替尼的重要中间体2-氨基-N-(2-氯-6-甲基苯基)噻唑-5-甲酰胺,总收率为81.3%。该方法合成路线短,原料价廉易得,反应收率高,生产成本低,避免使用易挥发的溴素以及会产生HCl的酰氯。2-Amino-N-（2-chloro-6-methylphenyl）thiazole-5-carboxamide, the key intermediate of dasatinib, was synthesized from 1,1,3,3-tetramethoxypropane via bromination with copper （II） bromide to give 2-bromo-1,1,3,3- tetramethoxypropane, followed by condensation and cyclization with thiourea to afford 2-aminothiazole-5-carbaldehyde, which was subjected to oxidative amidation with 2-chloro-6-methylaniline in the presence of cuprous bromide and tert- butylhydroperoxide. The overall yield was 81.3 %. This method provides several advantages such as short synthetic route, inexpensive and easily obtained raw materials, high yield and lower production costs, it also avoids using volatile bromine and acyl chloride.

关 键 词：2-氨基-N-(2-氯-6-甲基苯基)噻唑-5-甲酰胺 达沙替尼 中间体 合成方法 

分 类 号：R914.5[医药卫生—药物化学]