抗痛风药物febuxostat的合成

Synthesis of febuxostat,an anti gout drug

目的合成新型抗痛风药物febuxostat(1)。方法以羟基苯腈为原料,经硫代甲酰化得到对羟基硫代苯甲酰胺(3),3经环合得到2-(4-羟基苯基)-4-甲基-噻唑-5-羧酸乙酯(4),4与乌洛托品反应,得到中间体2-(3-甲酰基-4-羟基苯基)-4-甲基-噻唑-5-羧酸乙酯(5),之后再经醚化、氰化、水解得到目标产物(1)。结果与结论中间体及目标化合物的结构经1H-NMR和FAB-MS确证。该合成路线中使用的原料和试剂价廉易得,反应条件温和易控,操作简便。

Aim To synthesize novel anti gout drug febuxostat （1）. Methods 4-Hydroxybenzonitrile（2） as the starting material was transformed to 4-hydroxy-thiobenzamide（3） via thioformylation. And ethyl 2-（4-hy- droxyphenyl）-4-methylthiazole-5-carboxylate（4）, which was synthesized via cyclization from 3, was treated with hexamethylenetetramine to generate the intermediate ethyl 2-（ 3-formyl-4-hydroxyphenyl）-4- methylthiazole-5-carboxylate（5）. The target compound febuxostat（1 ） was obtained from 5 by etherification, cyanidation, hydrolysis. Results and conclusion The related structures of intermediates and product were identified by ^1H-NMR and FAB-MS. This improved procedure has several advantages of low consumption, mild condition, and convenient operation.