替诺福韦酯艾拉酚胺合成工艺改进  

Improvement of Synthetic Process of Tenofovir Alafenamide

作　　者：孔叶青 KONG Ye-qing(Zhejiang Menovo Pharmaceutical Chemistry Co.,Ltd.,Shangyu 312369,China)

机构地区：[1]浙江美诺华药物化学有限公司,浙江上虞312369

出　　处：《化工管理》2021年第17期148-149,共2页Chemical Engineering Management

摘　　要：文章以(R)-(1-(6-氨基-9H-嘌呤-9-基)丙烷-2-基氧基)甲基膦酸为起始原料,经过磷苯酯化、羟基氯代、磷酯酰胺化合成替诺福韦酯艾拉酚胺,最后与富马酸成盐得到API。中间体(R)-(1-(6-氨基-9H-嘌呤-9-基)丙烷-2-基氧基)甲基膦酰苯基酯经过羟基氯代和偶联酰胺化过程为一步合成,无需中间体提纯。与现有技术相比,该工艺路线简单,原料易得,产物收率高,纯度高,极大简化反应操作步骤,提高了生产效率。Using(R)-(1-(6-amino-9h-purine-9-yl)propane-2-yloxy)methyl phosphonic acid as starting material,tenofovir dipivoxileilaphenolamide was synthesized by phosphobenzene esterif ication,hydroxyl chlorination and phosphorylation.Finally,API was obtained by salt formation with fumaric acid.The intermediate(R)-(1-(6-amino-9h-purine-9-yl)propane-2-yloxy)methyl phosphonylphenyl ester was synthesized by hydroxyl chlorination and coupling amidation in one step without intermediate purif ication.Compared with the prior art,the process route is simple,the raw materials are easy to obtain,the product yield is high,the purity is high,the reaction operation steps are greatly simplif ied,and the production eff iciency is improved.

关 键 词：替诺福韦酯艾拉酚胺 合成 工艺改进 

分 类 号：TQ460[化学工程—制药化工]