非布司他合成工艺杂质问题研究

Research on the Impurities of Febuxostat

为控制非布司他原料药的质量,从非布司他原料药制备工艺中分离并鉴定了4个杂质,分别为2-(3-氨基甲酰基-4-异丁氧基苯基)-4-甲基-5-噻唑羧酸、2-(3-氰基-4-异丁氧基苯基)-4-甲基-5-噻唑羧酸、2-(3-甲酰基-4-异丁氧基苯基)-4-甲基-5-噻唑羧酸、2-[3-(羟基亚氨基)甲基-4-异丁氧基苯基]-4-甲基-5-噻唑羧酸。经核磁共振氢谱、质谱确证了这些工艺杂质的结构,分析了其产生的原因,并设计合成了这些杂质。

In order to control the quality of the raw materials of Febuxotast,four impurities were isolated and identified from the preparation processwith the names of 2-（3-carbamoyl-4-isobut-oxyphenyl）-4-methylthiazole-5-carboxylic acid,2-（3-cyanophenyl-4-（sec-butoxy））-4-methylthia-zole-5-carboxylic acid,2-（3-formyl-4-isobutoxyphenyl）-4-methylthiazole-5-carboxylic acid,and 2-（3-（（hydroxyimino）methyl）-4-isobutoxyphenyl）-4-methylthiazole-5-carboxylicacid.The structures of these impurities were confirmed by 1 HNMR and MS.The causes of the impurities were analyzed and the impurities were synthesized.