抗痛风药物febuxostat的合成

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。

Synthesis of febuxostat, an anti gout drug

Abstract：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-hydroxyphenyl）-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.