磷酸肌醇3-激酶δ抑制剂Idelalisib的合成工艺研究

Study on the synthesis technology of Idelalisib,the sel-ective inhibitor of PI3Kδ

目的磷酸肌醇3-激酶δ抑制剂Idelalisib的合成工艺研究。方法以2-氟-6-硝基苯甲酸为起始原料,通过缩合、硝基还原、缩合、脱水环合脱保护、取代和重结晶最终得到目标产物Idelalisib。结果本路线共5步反应,反应总收率为40.1%,终产品HPLC含量质量分数为99.9%。目标产物和部分中间体结构均经MS、1H-NMR和13C-NMR确证。结论该路线具有原料易得,反应条件温和,对环境污染较小,操作简单等优点,适合工业化生产。

Objective The research of synthesis process for Idelalisib,the Phosphoinositide 3-Kinase δ inhibitor.Methods The target product Idelalisib was finally got by condensation,nitro reduction,condensation,cyclization,deprotection,substitution,and recrystallization starting from 2-fluoro-6-nitrobenzoic acid.Results The route had 5 steps of reaction,the total reaction yield was 40.1%,and the final product HPLC purity was 99.9%.The target product and the part of the intermediates structures were confirmed by MS,1H-NMR and 13C-NMR.Conclusion The route has the advantages of easy availability of raw materials,mild reaction conditions,less environmental pollution,and simple operation,so it is suitable for industrialized production.