法莫替丁合成工艺改进  

Improved Synthesis Process of Famotidine

作　　者：王亮 WANG Liang(Shanghai Huilun Pharmaceutical Co.Ltd.,Shanghai 201100,China)

机构地区：[1]上海市汇伦医药股份有限公司,上海201100

出　　处：《安徽化工》2024年第1期102-107,共6页Anhui Chemical Industry

摘　　要：采用脒基硫脲和1,3-二氯丙酮环合反应制得2-(4-(氯甲基)噻唑-2-基)胍基盐酸盐,再与硫脲反应制得(S)-((2-胍基-4-噻唑基)甲基)异硫脲二盐酸盐,最后与N-硫酰胺基-3-氯丙脒盐酸盐反应生成法莫替丁。采用一锅法制备关键中间体2-(4-(氯甲基)噻唑-2-基)胍基盐酸盐,单步反应收率达到95%以上,合成法莫替丁的总收率达到60%,大大降低了法莫替丁的生产成本。(S)-(2-Guanidino-4-thiazolyl)methylisothiourea dihydrochloride was synthesized by reacting 1,3-dichloro-acetone with amidinothiourea in the acetone and reacting 2-(4-(chloromethyl)thiazol-2-yl)guanidine hydrochloride with thiourea.Finally,it reacts with N-thiamide-3-chlorpropamidine hydrochloride to form famotidine.In this process,the key intermediate 2-(4-(chloromethyl)thiazol-2-yl)guanidine hydrochloride is prepared by one-pot method.The yield of this reaction can reach more than 95%,and the total yield of synthetic famotidine can reach 60%,which great-ly reduces the production cost of Famotidine.

关 键 词：脒基硫脲 (S)-((2-胍基-4-噻唑基)甲基)异硫脲二盐酸盐 一锅法合成 

分 类 号：R914[医药卫生—药物化学]