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

作　　者：王天照 于文佳 刘改改 陈振花 任旭红[1] WANG Tianzhao;YU Wenjia;LIU Gaigai;CHEN Zhenhua;REN Xuhong(School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Shenyang 110016,China;Beijing New Leading Pharmaceutical Technology Development Co.,Ltd.,Beijing 100083,China;JOINN laboratories,Beijing 100176,China)

机构地区：[1]沈阳药科大学制药工程学院,辽宁沈阳110016 [2]北京新领先医药科技发展有限公司,北京100083 [3]北京昭衍新药研究中心股份有限公司,北京100176

出　　处：《沈阳药科大学学报》2020年第2期113-117,共5页Journal of Shenyang Pharmaceutical University

基　　金：辽宁省自然科学基金指导计划资助项目(201602712).

摘　　要：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.

关 键 词：磷酸肌醇3-激酶δ抑制剂 Idelalisib 合成工艺 

分 类 号：TQ463.5[化学工程—制药化工]