摘要
为控制米诺膦酸的质量,基于生产工艺确定其存在二聚体有关物质。采用2-(咪唑并[1,2-a]吡啶-3-基)乙酸为原料,仅使用单一磷酸化试剂三氯化磷,甲磺酸(5.5倍物质的量)作为反应溶剂,在温和条件下即实现了米诺膦酸二聚体,即[2,5-二羟基-3,6-双(咪唑[1,2-a]吡啶-3-基甲基)-2,5-二氧基-1,4,2,5-二氧二膦-3,6-二酰基]双(膦酸)的高效合成,收率达到50%以上,纯度不低于99.0%,结构经^(1)H NMR、^(13)C NMR、^(31)P NMR和HRMS确证,可作为米诺膦酸质量研究的对照品。
In order to control the quality of minodronic acid,this study determined the dimer,[2,5-dihydroxy-3,6-bis(imidazole[1,2-a]pyridin-3-ylmethyl)-2,5-dioxo-1,4,2,5-dioxodiphosphine-3,6-diacyl]bis(phosphonic acid),a relative substance of minodronic acid based on the production process of minodronic acid.It was obtained by the new strategy by reaction of 2-(imidazo[1,2-a]pyridin-3-yl)acetic acid with phosphorus trichloride in methanesulfonic acid(5.5 times amount of substance).The yield was more than 50%,and the purity was not less than 99.0%.The structure of the dimer was confirmed by ^(1)H NMR,^(13)C NMR,^(31)P NMR and high resolution mass spectrometry(HRMS),which could be used as a standard for the quality study of minodronic acid.
作者
朱冉冉
田天恩
王建耀
董志奎
ZHU Ranran;TIAN Tianen;WANG Jianyao;DONG Zhikui(Yangtze River Pharmaceutical Group Beijing Haiyan Pharmaceutical Co.,Ltd.,Beijing 102206)
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2022年第4期474-476,共3页
Chinese Journal of Pharmaceuticals
关键词
米诺膦酸
有关物质
质量控制
二聚体
结构确证
minodronic acid
relative substance
quality control
dimer
structure confirmation
