4-氨基-2-甲基-10H-噻吩[2,3-b][1,5]-苯二氮盐酸盐的合成

Synthesis of 4-Amino-2-methyl-10H-thiene[2,3-b][1,5]benzodiazepine Hydrochloride

4-氨基-2-甲基-10H-噻吩[2,3-b][1,5]-苯二氮盐酸盐是合成治疗精神分裂症药物奥氮平的关键中间体。本文以2-(2-硝基苯胺基)-5-甲基噻吩-3-腈为原料,在酸性条件下,用金属锡粉作还原剂,微量的氯化亚锡二水合物作催化剂,制备得到4-氨基-2-甲基-10H-噻吩[2,3-b][1,5]-苯二氮盐酸盐。整个还原反应过程中,氯化亚锡不断循环,避免有毒氯化亚锡溶液的大量使用,符合绿色化学的概念。使用锡粉还原(化合价从0价到+4价),与氯化亚锡(化合价从+2价到+4价)相比,摩尔使用量减半,并且后处理简单,污染少,成本低,适宜工业化推广。

4-Amino-2-methyl-10H-thiene[2,3-b][1,5]benzodiazepine hydrochloride is a key intermediate in the synthesis of olanzapine for the treatment of schizophrenia.4-Amino-2-methyl-10H-thiene[2,3-b][1,5]benzodiazepine hydrochloride is prepared from 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile with metal tin powder as reducing agent and trace stannous chloride dihydrate as catalyst under acidic conditions.Throughout the reduction reaction,stannous chloride is constantly cycled to avoid the extensive use of toxic stannous chloride solution,conforming to the concept of green chemistry.Using tin powder reduction(valence from 0 to+4),the molar usage is halved compared to stannous chloride(valence from+2 to+4),which is suitable for industrial promotion,with simple post-treatment,less pollution and low cost.