拉罗替尼的合成工艺优化  

Synthesis Process Optimization of Larotrectinib

作　　者：郝林林 蔡志强[1] 李帅 HAO Lin-lin;CAI Zhi-qiang;Li Shuai(Liaoning Province Professional and Technical Innovation Center for Fine Chemical Engineering of Aromatics Downstream, School of Petrochemical Engineering, Shenyang University of Technology, Liaoyang 111003, China;Key Laboratory for Chemical Drug Research of Shandong Province, Instiitute of Phamaceutical Sciences of Shandong Province, Jinan 250101, China)

机构地区：[1]沈阳工业大学石油化工学院辽宁省芳烃下游精细化工专业技术创新中心,辽宁辽阳111003 [2]山东省药学科学院,化学药物重点实验室,山东济南250101

出　　处：《合成化学》2021年第9期786-789,共4页Chinese Journal of Synthetic Chemistry

基　　金：辽宁省自然科学基金资助项目(20180550016);辽宁省教育厅科学研究项目(LJGD2020015)。

摘　　要：以(R)-2-(2,5-二氟苯基)吡咯烷和5-氯-3-硝基吡唑并[1,5-a]嘧啶为起始原料,经胺化,还原,再与氯甲酸苯酯酰化,最后与(S)-3-羟基吡咯烷反应成盐后得到拉罗替尼,总收率为73.34%。其结构经^(1)H NMR、IR及ESI-MS确证,并探讨了中间体和目标化合物合成工艺的影响因素。(R)-2-(2,5-difluorophenyl)pyrrolidine and 5-chloro-3-nitropyrazolium[1,5-a]pyrimidine were used as starting materials to synthesis larotrectinib by amination,reduction,acylation with phenyl chloroformate,and finally reaction with(S)-3-hydroxy pyrrolidine,the total yield was 73.34%.The structure was characterized by ^(1)H NMR,IR and ESI-MS.Meanwhile,the factors affecting on the synthesis process of the intermediate and target compounds were discussed.

关 键 词：拉罗替尼 抗肿瘤 工艺优化 吡唑并嘧啶 合成 

分 类 号：O621.25[理学—有机化学]