抗乙肝药物恩替卡韦的合成工艺改进  

Improvement of synthesis process of Antihepatitis B drug entecavir

作　　者：王乔 刘骞峰 WANG Qiao;LIU Qianfeng(School of Chemistry and Chemical Engineering Xi'an University of Architecture and Technology,Xi'an 710000 Shaanxi China;Xi􀆳an Ruilian New Material Co.Ltd,Xi'an 710000 Shaanxi China)

机构地区：[1]西安建筑科技大学化学与化工学院,陕西西安710000 [2]西安瑞联新材料股份有限公司,陕西西安710000

出　　处：《化学研究》2020年第5期416-420,共5页Chemical Research

摘　　要：以化合物(1S,2S,3S,5S)⁃5⁃[2⁃[(4⁃甲氧基苯基)二苯甲基]氨基]⁃6⁃(苯甲氧基)⁃9⁃H⁃嘌呤⁃9⁃基⁃3⁃(苯甲氧基)⁃2⁃[(苯甲氧基)甲基]⁃1⁃环戊醇为该研究的起始原料,经N⁃烷基化、氧化、亚甲基化、水解、酸解五步反应合成恩替卡韦,并对过程中的工艺条件进行改进.与原反应工艺相比,操作简便,副产物少,同时缩短了反应周期,对设备要求低,更适合工业化生产.Entecavir was prepared from the intermediate(1S,2S,3S,5S)⁃5⁃[2⁃[(4⁃methoxyphenyl)diphenylmethyl]amino]⁃6⁃(Benzoxy)⁃9⁃H⁃purin⁃9⁃yl⁃3⁃(Benzoxy)⁃2⁃[(Benzoxy)methyl]⁃1⁃cyclope⁃anntanol by N⁃alkylation,oxidation,methylation,hydrolysis and acidolysis.The process conditions were improved.Compared with the original reaction process,it is more suitable for industrial production because of simple operation,less by⁃products,shorter reaction period and lower equipment requirements.

关 键 词：恩替卡韦 核苷类药物 工艺改进 

分 类 号：TQ463[化学工程—制药化工]