富马酸卢帕他定的合成方法  

The Synthesis of Rupatadine Fumarate

作　　者：张丽君[1,2] 陈海鹏 

机构地区：[1]扬子江药业集团有限公司海外部,江苏泰州225321 [2]东南大学经济管理学院,江苏南京210096 [3]江苏国丹生物制药有限公司总经办,江苏泰州225321

出　　处：《广东化工》2016年第24期49-50,共2页Guangdong Chemical Industry

摘　　要：富马酸卢帕他定是一种兼具有抗组胺和PAF拮抗活性的三环类抗过敏药物,临床应用广泛。虽然已有多篇有关其合成方法的文献报道,但是均存在路线较长、后处理繁琐或安全性问题。文章以廉价易得的3,5-二甲基吡啶为起始原料,通过溴代、缩合及富马酸成盐三步反应,以21%的总收率完成了富马酸卢帕他定的合成。所得产品纯度大于99.6%,单个杂质均小于0.1%。此合成工艺稳定、重现性良好,适合于工业化生产。Rupatadine fumarate is a tricyclic antianaphylaxis drug, which can be used as histamine antagonists and PAF inhibitor simultaneously. It has been used extensively in clinical application for many years, though there are several literature reports about its synthesis, the long synthesis steps and the safety problems limit their industrial application. In the article, the 3,5-dimethyl-pyridine was chosen as the starting material, Bromination, condensation, salify with fumaric acid completed the synthesis of rupatadine fumarate with 21 % overall yield in three steps. The purity is more than 99.6 %, and the maximum impurity is less than 0.1 %. The synthetic procedure is stability, reproducible and suitable for the industrial production.

关 键 词：富马酸卢帕他定 合成 缩合 

分 类 号：TQ225.152[化学工程—有机化工]