Janus激酶抑制剂Momelotinib的合成  

Synthesis of Janus Kinase Inhibitor Momelotinib

作　　者：肖金阳 王刚 张帆 XIAO Jinyang;WANG Gang;ZHANG Fan(College of Pharmacy,Jinzhou Medical University,Jinzhou 121001,China)

机构地区：[1]锦州医科大学药学院,辽宁锦州121001

出　　处：《合成化学》2024年第6期556-561,共6页Chinese Journal of Synthetic Chemistry

基　　金：辽宁省自然科学基金资助项目(2019-ZD-0834)。

摘　　要：Momelotinib是Janus激酶的选择性抑制剂,用于治疗中高风险骨髓纤维化。为了解决现有合成方法存在的成本高、反应条件严苛、收率偏低和废料对环境污染严重等问题,以1-氟-4-硝基苯为起始原料,经取代、还原、Pinner、与DMF-DMA缩合、环合、水解和酰化反应合成目标化合物Momelotinib,总收率为55.04%,纯度为99.45%。Momelotinib的化学结构经~1H NMR、^(13)C NMR和MS(ESI)确证。上述合成路线试剂成本低、操作简便、收率高且绿色环保,适合工业化生产。Momelotinib is a selective Janus kinase inhibitor and can be used to treat moderate or high-risk myelofibrosis. In order to solve the problems of reported synthetic methods such as high cost, strict reaction conditions, low yield and serious environmental pollution, using 1-fluoro-4-nitrobenzene as the starting material, the target compound Momelotinib was synthesized by substitution, reduction, Pinner, condensation with DMF-DMA, cyclization, hydrolysis and acylation reactions. The total yield was 55.04% and the purity was 99.45%. The chemical structure of Momelotinib was confirmed by 1 H NMR , 13 C NMR and MS (ESI). The above synthetic route showed the characteristics of low reagent cost, simple operation, high yield and environmental friendly, which is suitable for industrial production.

关 键 词：Momelotinib Janus激酶抑制剂 骨髓纤维化 2-氨基嘧啶化合物 合成 

分 类 号：O625[理学—有机化学]