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目的改进抗肿瘤药马赛替尼(1)的合成工艺。方法以2-甲基-5-硝基苯胺为原料,与硫氰酸铵和乙酰氯的反应产物发生加成反应得硫脲化合物5,5与自制的2-溴-1-(吡啶-3-基)乙酮氢溴酸盐(2)环合成噻唑化合物6,6还原后与自制的酰氯化合物3反应成酰胺得马赛替尼(1)。结果总收率为28.0%(以2-甲基-5-硝基苯胺计),各步关键中间体及目标物结构经MS和1H NMR确证。结论改进后的方法简化了操作,降低了成本,适合于工业化生产。
Objective To improve the synthesis of antitumor drug maitinib (1). Methods The reaction of 2-methyl-5-nitroaniline with the reaction product of ammonium thiocyanate and acetyl chloride gave thiourea compound 5,5 and 2-bromo-1- (pyridin-3 - yl) ethanone hydrobromide (2) Ring-forming thiazole compound 6,6 After reduction, it is reacted with self-made acid chloride compound 3 to give amide (1). The overall yield was 28.0% (based on 2-methyl-5-nitroaniline). The key intermediates and target structures of each step were confirmed by MS and 1H NMR. Conclusion The improved method simplifies operation, reduces costs and is suitable for industrial production.