盐酸西那卡塞中间体有关物质的制备及纯化  

Preparation and Purification of Related Substances of Cinacalcet Hydrochloride

作　　者：王栋 龙玺国 郑建东[1] 徐琳寓 王崇益 马玉恒 WANG Dong;LONG Xi-guo;ZHENG Jian-dong;XU Lin-yu;WANG Chong-yi;MA Yu-heng(College of Material and Chemical Engineering,Chuzhou University,Chuzhou 239000,China;Production Technology Department,Jiangsu Runan Pharmaceutical CO.,LTD.Huaiʼan 223001,China)

机构地区：[1]滁州学院材料与化学工程学院,安徽滁州239000 [2]江苏润安制药有限公司生产技术部,江苏淮安223001

出　　处：《广州化学》2020年第6期36-40,62,共6页Guangzhou Chemistry

基　　金：滁州学院科研启动资金资助项目(2020qd09)。

摘　　要：为实现西那卡塞中间体XNKS-02的质量控制,避免原料SM2在N,Nʼ-羰基二咪唑(CDI)作用下缩合成副产物XNKS-02-P,导致XNKS-02产率降低,以(R)-(+)-1-(1-萘基)乙胺为原料,与CDI在二氯甲烷中发生缩合反应、制备色谱分离得到化合物XNKS-02-Pʼ。XNKS-02-Pʼ经HPLC定位比对与XNKS-02-P的保留时间一致,再经1H-NMR、13C-NMR和MS确证,合成的XNKS-02-Pʼ即为XNKS-02-P。新方法合成的XNKS-02-Pʼ可作为定量标准品,用以定量分析XNKS-02生产中副产物XNKS-02-P。The byproduct XNKS-02-P was synthesized by SM2 under the action of CDI,which led to the reduction of XNKS-02 yield.The quality control of XNKS-02 was realized by reducing the generation of by-product.The impurity XNKS-02-Pʼwas synthesized from(R)-(+)-1-(1-naphthalene)ethylamine by condensation with N,Nʼ-carbonyldiimidazole in dichloromethane.Then it was separated by preparation chromatography.Through HPLC localization comparison,it was found that the retention time of the impurity XNKS-02-Pʼwas consistent with that of the impurity XNKS-02-P.Then,the structure of impurity XNKS-02-Pʼwas confirmed by 1H-NMR,13C-NMR and MS.Thus,it was determined that the synthesized impurity XNKS-02-Pʼwas XNKS-02-P.XNKS-02-Pʼcould be used as reference materials,which was synthesized by the new method.It was used for quantitative analysis of xnks-02-p which was the byproduct of xnks-02.

关 键 词：西那卡塞中间体酰胺(XNKS-02) 缩合反应 N Nʼ-羰基二咪唑 合成 

分 类 号：R914[医药卫生—药物化学]