非布索坦的合成

Synthesis of Febuxostat

设计完成两条非布索坦(1)的合成路线。以对羟基苯甲酸甲酯为原料,经过溴化、醚化得到关键中间体3-溴-4-(2-甲基丙氧基)苯甲酸甲酯(9)。第一条合成路线将9与氰化亚铜反应引入氰基,然后合成噻唑环,最后经水解得到1,总收率为35%:第二条合成路线将9合成噻唑环,然后引入氰基,水解后得到1,总收率为38%。

Two novel synthetic methods of febuxostat were reported. The key intermediate methyl 3-bromo- 4-（isobutoxy） benzoate （9） was prepared from starting material methyl 4-hydroxybenzoate via bromination and etherization. In the first method, compound 9 was treated with CuCN, followed by thiazole ring formation to give febuxostat in 35 % overall yield. In the second method, thiazole ring was initially formed, then introduced the cyano group in 38 % overall yield.