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.

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)