降压新药西尼地平杂质Ⅰ的制备  

Preparation of impurity Ⅰ of antihypertensive drug clinidipine

作　　者：傅鹏 苏伟[1] 王学元 李晶 孙艳[3] FU Peng;SU Wei;WANG Xueyuan;LI Jing;SUN Yan(School of Chemical Engineering and Technology,Tianjin University,Tianjin 300072,China;Increase(Tianjin)Innovative Medicine,Tianjin 300385,China;Department of Chemistry,School of Sciences,Tianjin University,Tianjin 300072,China)

机构地区：[1]天津大学化工学院,天津300072 [2]盈科瑞(天津)创新医药研究有限公司,天津300385 [3]天津大学理学院化学系,天津300072

出　　处：《精细化工》2021年第5期1068-1073,共6页Fine Chemicals

摘　　要：以西尼地平为起始原料,活化MnO_(2)为氧化剂,一步法制备了2,6-二甲基-4-(3-硝基苯基)吡啶-3,5-二甲酸3-(2-甲氧基)乙酯5-(3-苯基)-2(E)-丙烯酯(记为西尼地平杂质Ⅰ)。经实验优化,制备西尼地平杂质Ⅰ的最适宜条件为:m(西尼地平)∶m(MnO_(2))=1.00∶1.24,甲苯为溶剂,105℃下反应1 h。反应得到西尼地平杂质Ⅰ收率为92.3%,经高效液相色谱面积归一化法检测后,纯度达到99.2%。产物结构经HRMS,^(1)HNMR、^(13)CNMR以及FTIR进行确认。该反应实现了西尼地平绿色高效直接转化西尼地平杂质Ⅰ。2,6-Dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate 3-(2-methoxy)ethyl 5-(3-phenyl)-2(E)-acrylic(impurityⅠof cilnidipine) was synthesized by one-step method from cilnidipine using activated MnO_(2) as oxidant. The reaction conditions were optimized. The optimal conditions were obtained as follows: m(cilnidipine)∶m(MnO_(2))=1.00∶1.24, toluene as solvent, reaction temperature of 105 ℃ and reaction time of 1 h. Under the above-mentioned conditions, the product with a yield of 92.3% and a purity of 99.2%(by the HPLC area normalization method) was obtained. The structure of the product was confirmed by ^(1)HNMR, ^(13)CNMR, HRMS and FTIR. This reaction realized green, efficient and direct transformation from cilnidipine to cilnidipine impurityⅠ.

关 键 词：西尼地平 MnO_(2) 西尼地平杂质Ⅰ 芳构化 精细化工中间体 

分 类 号：O626.3[理学—有机化学] TQ460.1[理学—化学]