目的 尋找一條合成尿酸轉(zhuǎn)運體1(URAT1)抑制劑RDEA3170的實用的合成路線。方法 利用3-溴-4-氯吡啶和1,4-二溴萘作為起始原料來合成RDEA3170,并著重研究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步關(guān)鍵反應(yīng)的反應(yīng)條件。結(jié)果 經(jīng)6步反應(yīng)合成了RDEA3170,并利用MS和¹H-NMR確證了結(jié)構(gòu),此路線總收率為16%;同時得到了上述3個關(guān)鍵步驟的最優(yōu)化的反應(yīng)條件。結(jié)論 得到了一條合成RDEA3170的實用路線。

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.

國家自然科學基金資助項目(21302141);天津市應(yīng)用基礎(chǔ)與前沿技術(shù)研究計劃項目(14JCQNJC12900)