4-氯-3-(三氟甲基)苯异氰酸酯及其衍生物索拉菲尼的合成

Synthesis of 4-chloro-3-trifluoromethylaniline and sorafenib

本文以邻氯三氟甲苯为起始原料,经混酸硝化,催化氢化,与BTC在1,2-二氯乙烷和1,4-二氧六环的混合溶剂中回流制得4-氯-3-(三氟甲基)苯异氰酸酯(三步总收率87.4%),再与4-(4-氨基苯氧基))-2-(甲基氨甲酰基)吡啶缩合成脲,制得抗肿瘤药物索拉菲尼,总收率为:84.0%,纯度:99.1%。

The target product was prepared from p-Chlorobenzotrifluoride（1）,which was transformed into the corresponding isocyanate（4） by mixed acid nitration,catalytic hydrogenation,and refluxed with BTC in the solution of 1,2-dichloroethane and 1,4-dioxare（the total yield of three steps was 87.4%）,then 4 reacted with 4-（4-aminophenoxy）-N-methyl-2-pyridinecarboxamide（5） to give the unsymmetrical diaryl urea sorafenib（6） as antitumor agent,the total yield was 84.0%,purity 99.1%.