RDEA3170的合成工艺研究  

Synthesis of RDEA3170

作　　者：张宪生[1,2] 刘钰强 谢亚非[1] 李川[1] 辛晓[1,3] 徐为人[1] 汤立达[1] 赵桂龙[1] 

机构地区：[1]天津药物研究院天津市新药设计与发现重点实验室,天津300193 [2]山东大学化学与化工学院,山东济南250100 [3]天津中医药大学研究生院,天津300193

出　　处：《现代药物与临床》2015年第10期1179-1184,共6页Drugs & Clinic

基　　金：国家自然科学基金资助项目(21302141);天津市应用基础与前沿技术研究计划项目(14JCQNJC12900)

摘　　要：目的寻找一条合成尿酸转运体1(URAT1)抑制剂RDEA3170的实用的合成路线。方法利用3-溴-4-氯吡啶和1,4-二溴萘作为起始原料来合成RDEA3170,并着重研究1,4-二溴萘合成4-溴-1-萘腈(3)、化合物3合成(4-氰基萘-1-基)硼酸(4)和Suzuki偶合3步关键反应的反应条件。结果经6步反应合成了RDEA3170,并利用MS和1H-NMR确证了结构,此路线总收率为16%;同时得到了上述3个关键步骤的最优化的反应条件。结论得到了一条合成RDEA3170的实用路线。Objective To find a practical synthetic route of uric acid transporter 1（URAT1） inhibitor RDEA3170. Methods 3-Bromo-4-chloropyridine and 1,4-dibromonaphthalene were used as starting materials. Three key synthetic steps, synthesis of 4-bromo-1-naphthonitrile（3）, synthesis of（4-cyanonaphthalen-1-yl）boronic acid（4） from compound 3, and the Suzuki coupling, were studied for the optimal reaction conditions. Results RDEA3170 was synthesized by 6 steps. The target compound was synthesized and characterized by MS, and 1H-NMR. The overall yield of this route was 16%. The reaction conditions of the three key steps were optimized. Conclusion A practical synthetic route of RDEA3170 is obtained.

关 键 词：RDEA3170 lesinurad URAT1抑制剂 合成工艺 高尿酸血症 痛风 

分 类 号：R914[医药卫生—药物化学]