极光激酶小分子抑制剂AT9283的合成

Synthesis of AT9283,an inhibitor of small molecular Aurora kinase

目的:合成极光激酶抑制剂AT-9283。方法:以3,4-二硝基苯甲酸为原料,经酰胺化,还原,关环,得到关键中间体5-吗啉基-4-甲基-2-(4-硝基-1H-3-吡唑基)-1H-苯并咪唑(4),4经还原后再与环丙胺成脲制得AT-9283。结果和结论:目标产物结构经IR,1H-NMR,13C-NMR和ESI-MS确证。本合成路线条件温和,操作简单,总收率较高,而且整个过程不需要柱色谱纯化。

Objective： To synthesize AT-9283, an Aurora kinase inhibitor. Methods： The intermediate 5- morpholin-4-ylmethyl-2-（4-nitro-1H-pyrazol-3-yl） -1H-benzimidazole （ 4 ） was prepared by amidation, reduction and cyclization with 3,4-dinitrobenzoic acid as the starting compound. AT-9283 was produced by urea formation. Results and Conclusion： The structure of AT9283 was verified by IR, 1H-NMR, 13C-NMR and ESI-MS. The pragmatic synthesis method with mild reactive conditions is simple and highly productive, and the preparation has no need of column chromatography.