甲磺酸伊马替尼的合成新方法

A new synthetic method of imatinib mesylate

目的探索甲磺酸伊马替尼的新合成方法。方法以2-硝基-4-碘甲苯为起始原料,经还原、加成、环合、缩合及成盐共5步反应得到目标产物甲磺酸伊马替尼。中间体3-二甲氨基-1-(3-吡啶基)-2-丙烯-1-酮是由3-乙酰吡啶经缩合制得;中间体4-((4-甲基哌嗪-1-基)甲基)苯甲腈是由4-(溴甲基)苯甲腈经烃化反应制得。结果与结论甲磺酸伊马替尼及其中间体的结构经HRMS、1H-NMR和13C-NMR谱确证。新合成路线采用并联式反应,极大地减少了反应步骤,反应操作简单、成本较低、可控性好,路线总收率为78.4%(以2-硝基-4-碘甲苯计),对工业化生产具有重要的参考价值。

Imatinib mesylate is used in the treatment of CML/GIST as a tyrosine kinase inhibitor. In this paper,a new synthetic route had been established based on the literatures. Starting from 2-nitro-4-iodotoluene,imatinib mesylate was synthesized through five steps,including reduction,addition,cyclization,condensation and salt formation. The total yield was 78.4%(based on the molar mass of 2-nitro-4-iodotoluene). The structures of intermediates and target compounds were confirmed by HRMS,1H-NMR,and 13C-NMR spectra. The process was scalable for industrial production for its advantages of available raw materials,facile operation,relatively lower cost,and high yield.■.