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

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.