伊曲康唑重要中间体的合成新方法

A Novel Synthetic Route for the Key Intermediate of Itraconazole

N^2-(2-丁基)甲酰肼与4-[[4-(4-羟基苯基)-1-哌嗪基]苯基]氨基甲酸苯酯(3)缩合,制得伊曲康唑重要中间体4-[4-[4-(羟基苯基)-1-哌嗪基]苯基]-2,4-二氢-2-(1-甲基丙基)-3H-1,2,4-三唑-3-酮,收率61.1%,纯度99.68%。该反应中,化合物3的酚羟基不需保护,减少了脱保护步骤,避免了强酸的使用;并且在构建三唑酮环之前引入仲丁基,避免了收率较低的丁基化反应。

The key intermediate of itraconazole, 4-[[4-（4-hydroxyphenyl）piperazin-1-yl] phenyl]-2,4-dihydro- 2-（1-methylpropyl）-3H-1,2,4-triazol-3-one was prepared via condensation of N2- （2-butyl）formohydrazide and phenyl 4- [[4- （4-hydroxyphenyl） piperazin-1-yl] phenyl] carbamate （3） with a yield of 61.1%, and a purity of 99.68 %. In this novel synthetic route, the phenolic hydroxyl of compound 3 didn＇t need to be protected, so that the de-protection by strong acid was avoided. Besides, the introducing ofsec-butyl before the building of triazole ring could save the butylation （with low yield） successfully. This new method is more suitable for industrial production.