丁酸氯维地平中四种杂质的合成  

Synthesis of four impurities of clevidipine butyrate

作　　者：宋志勇[1] 沈国兵[1] 刘艳华[2] 邢俊德[1] 

机构地区：[1]太原理工大学化学化工学院,山西太原030024 [2]中国药科大学生命科学与技术学院,江苏南京210009

出　　处：《中国药物化学杂志》2015年第4期295-297,共3页Chinese Journal of Medicinal Chemistry

基　　金："重大新药创制"科技重大专项资助项目(2012ZX09202101-001)

摘　　要：目的为加强对丁酸氯维地平原料药的质量控制,合成丁酸氯维地平的四种杂质。方法以合成的丁酸氯维地平和其中间体4-(2,3-二氯苯基)-2,6-二甲基-1,4-二氢-3,5-吡啶二羧酸单甲酯(1)为原料,1经脱羧合成杂质A,杂质A经氧化合成杂质B;同样以1为原料,经水解、酯化合成杂质D;丁酸氯维地平经氧化合成杂质C。结果与结论所合成的杂质结构经1H-NM R和M S确证,纯度经HPLC确证在98%以上。合成的丁酸氯维地平杂质可作为丁酸氯维地平原料药质量控制的杂质对照品。Clevidipine butyrate is the first intravenous dihydropyridine calcium-channel blocker. To improve the quality control of clevidipine butyrate, four impurities （ A, B, C, D ） were synthesized. The target compounds were obtained from clevidipine butyrate and its intermediate 4- （2,3-dichlorophenyl） -2,6-methyl-l, 4-dilaydropyridine-3-methoxycarbonyl-5-carboxylic acid （1）. Impurity A was obtained by decarboxylation from compound 1, and impurity B was prepared by further oxidation of A. Impurity C was synthesized via oxidation of clevidipine butyrate, and impurity D was obtained by hydrolysis and esterification from compound （1）. Their structures were confirmed by ^1H-NMR and MS, and their purities were over 98% via HPLC detection. The four impurities can be used as reference substances in the quality control of clevidipine butyrate.

关 键 词：丁酸氯维地平 杂质 合成 

分 类 号：R914.5[医药卫生—药物化学]