伊班膦酸钠中间体杂质的制备与结构表征  

Preparation and Structural Characterization of Impurities in the Intermediate of Ibandronate Sodium

作　　者：褚海龙 陈丽娜[2] 梁云科 CHU Hailong;CHEN Lina;LIANG Yunke(Lesheng Pharmachutical Shijiazhuang Co.,Ltd.;Hebei Hospital of Traditional Chinese Medicine Department,Shijiazhuang 050000)

机构地区：[1]乐声药业石家庄有限公司 [2]河北省中医院,石家庄050000

出　　处：《化工生产与技术》2025年第2期7-12,I0002,共7页Chemical Production and Technology

摘　　要：分析了伊班膦酸钠的3条合成路线,以3-甲胺基丙腈和1-溴戊烷为起始物料经过缩合、水解、膦酸化反应得到伊班膦酸钠的路线具有流程短、成本低和安全性好等优点。然而,在该路线的缩合步骤得到中间体3-(N-甲基-N-正戊胺基)丙腈的过程中,易产生较多杂质A,影响产品质量。通过对化学合成的杂质A的核磁共振(NMR)波谱(^(1)H-NMR、^(13)C-NMR和DEPT)和二维NMR波谱(COSY、HSQC和HMBC)的解析,对其NMR信号进行了归属,确认了杂质A的构型。Three synthetic routes of sodium ibandrophosphate were analyzed.The route of obtaining sodium ibandrophosphate from 3-methylaminopropane and 1-bromopentane as starting materials through condensation,hydrolysis,and phosphorylation reactions has the advantages of short process,low cost,and good safety.However,during the condensation step of this route to obtain intermediate 3-(N-methyl-N-n-amylamine)propionitrile,a significant amount of impurity A is easily generated,which affects the product quality.By analyzing the nuclear magnetic resonance(NMR)spectra(^(1)H-NMR,^(13)C-NMR,and DEPT)and two-dimensional NMR spectra(COSY,HSQC,and HMBC)of impurity A synthesized chemically,the NMR signals were assigned and the configuration of impurity A was confirmed.

关 键 词：伊班膦酸钠 中间体 杂质 核磁共振 结构确证 

分 类 号：TQ225.53[化学工程—有机化工]