目的 尋找一條合成尿酸轉運體1(URAT1)抑制劑lesinurad的實用的合成路線。方法 利用1-溴萘和環(huán)丙基溴化鎂作為起始原料, 經(jīng)過10步反應合成了目標化合物lesinurad, 并著重研究了由中間體4-環(huán)丙基-1-萘基異硫氰酸酯(4)合成中間體3-氨基-4-(4-環(huán)丙基萘-1-基)-1H-1,2,4-三唑-5(4H)-硫酮(7)的方法。結果 合成了目標化合物, 并利用IR、MS和¹H-NMR確證了結構, 此路線所得產(chǎn)品收率為18.2%, 質(zhì)量分數(shù)為99.17%。同時得到了一條由化合物4合成化合物7的新路線, 大幅度提高了合成化合物7的收率。結論 得到了一條合成lesinurad的實用路線, 并獲得了一種產(chǎn)率更高的合成重要中間體7的新方法。

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.

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