4-(吡啶-3-基)-2-[(2-甲基-5-氨基苯基)氨基]噻唑的合成

Synthesis of 4-(Pyridin-3-yl)-2-[(2-methyl-5-aminophenyl)amino]thiazole

1-(吡啶-3-基)乙酮与离子液体[bmim]Br_3常温发生溴化反应,然后与硫氰酸铵发生取代反应,再与2-甲基-5-硝基苯胺在乙酸作用下加成环化"一锅法"得到4-(吡啶-3-基)-2-[(2-甲基-5-硝基苯基)氨基]噻唑,进而在Pd-Fe/TiO_2催化下常压氢化得到马赛替尼关键中间体4-(吡啶-3-基)-2-[(2-甲基-5-氨基苯基)氨基]噻唑,总收率为87%。方法简便,收率高,离子液体[bmim]Br_3的反应产物[bmim]Br可用作后续反应的催化剂和溶剂,且可回收利用。

4-（Pyridin-3-yl）-2-[（2-methyl-5-aminophenyl）amino]thiazole, the key intermediate of masitinib, was synthesized from 1-（pyridin-3-yl）ethanone by bromination with ionic liquid 1-butyl-3-methylimidazolium tribromide（[bmim]Br_3） at room temperature, substitution with ammonium thiocynate and cyclization with 2-methyl-5-nitroaniline in the presence of acetic acid in one-pot to give 4-（pyridin-3-yl）-2-[（2-methyl-5-nitrophenyl）amino]thiazole, which was subjected to hydrogenation catalyzed by Pd-Fe/TiO_2 under atmospheric pressure with an overall yield of 87%. The ionic liquid [bmim]Br generated by [bmim]Br_3 acted as the catalyst and solvent for the following reactions and can be recycled.