[关键词]
[摘要]
目的 寻找一条合成尿酸转运体1(URAT1)抑制剂lesinurad的实用的合成路线。方法 利用1-溴萘和环丙基溴化镁作为起始原料, 经过10步反应合成了目标化合物lesinurad, 并着重研究了由中间体4-环丙基-1-萘基异硫氰酸酯(4)合成中间体3-氨基-4-(4-环丙基萘-1-基)-1H-1,2,4-三唑-5(4H)-硫酮(7)的方法。结果 合成了目标化合物, 并利用IR、MS和1H-NMR确证了结构, 此路线所得产品收率为18.2%, 质量分数为99.17%。同时得到了一条由化合物4合成化合物7的新路线, 大幅度提高了合成化合物7的收率。结论 得到了一条合成lesinurad的实用路线, 并获得了一种产率更高的合成重要中间体7的新方法。
[Key word]
[Abstract]
Objective To find a practical synthetic route of uric acid transporter 1 (URAT1) inhibitor lesinurad. Methods 1-Bromonaphthalene and cyclopropylmagnesium bromide were used as starting materials. The target compound lesinurad was synthesized by 10 steps. The synthetic route of the intermediate 3-amino-4-(4-cyclopropylnaphthalen-1-yl)-1H-1,2,4-triazole-5(4H)-thione (7) starting from 4-cyclopropylnaphthalen-1-yl isothiocyanate (4) was studied with expectation of improving yield. Results The target compound was synthesized and characterized by IR, MS, and 1H-NMR. The overall yield of this route was 18.2%, and the purity was 99.17%. A new synthetic route of compound 7 starting from compound 4 was developed with significantly improved yield. Conclusion A practical synthetic route of lesinurad is obtained. A new synthetic route of the key intermediate 7 is developed with significantly improved yield.
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[基金项目]
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)