摘要:
目的 改进甲磺酸伊马替尼的合成工艺。 方法 以4-[(4-甲基哌嗪-1-基)甲基]苯甲酰氯二盐酸盐与4-甲基-N3-[4-(3-吡啶基)嘧啶-2-基]-1,3苯二胺为起始原料,进行水相缩合反应得到伊马替尼游离碱,再与甲磺酸成盐,两步反应合成新型酪氨酸酶抑制剂类抗肿瘤药物伊马替尼。 结果 优化后的工艺成本低廉、后处理简便、产品纯度高、收率高,并且对环境污染小。纯度可达99.7%,且单一杂质<0.1%。 结论 新工艺的总收率达81.5%,可工业化生产,前景广阔。目标产物结构经1H NMR,ESI-MS得到结构确证。
Abstract:
Objective To obtain the improved synthesis of imatinib mesylate. Methods 4-[(4-methyl-piperazin-1-yl) methyl] benzoyl chloride dihydrochloride and 4-methyl-N3-[4-(3-pyridyl) pyrimidin-2-yl]-1,3-phenylenediamine were used as starting raw material to perform a condensation reaction in the aqueous phase to give imatinib free base, which was then neutralized with methanesulfonic acid to obtain the novel antineoplastic tyrosinase inhibitor imatinib mesylate by the use of a two-step reaction. Results The improved synthesis was considered to have the advantages of low cost, easy post-processing, high purity, high yield and environmental pollution with the HPLC purity≥99.7% and the single impurity<0.1%. Conclusion The total yield of the novel method was 81.5%, having an enough broad industrial production prospect.The targeted compound structure was confirmed by 1H NMR and ESI-MS.
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