(R)-1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-5-甲氧羰基-3-吡啶羧酸的合成  

Synthesis of (R)-2,6-dimethyl-4-(3-nitrophenyl)-5-(methoxycarbonyl)-1,4-dihydropyridine-3-carboxylic Acid

作　　者：王建塔[1,2] 张吉泉 毛远湖[1] 汤磊 WANG Jian-ta;ZHANG Ji-quan;MAO Yuan-hu;TANG Lei(Guizhou Medical University,Guizhou Guiyang 550004;Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D,Guizhou Guiyang 550004,China)

机构地区：[1]贵州医科大学,贵州贵阳550004 [2]贵州省化学合成药物研发利用工程技术研究中心,贵州贵阳550004

出　　处：《广州化工》2019年第22期53-55,共3页GuangZhou Chemical Industry

基　　金：贵州省研究生教育教学改革重点课题(黔教合YJSCXJH[2018]019);贵州省科技计划社会攻关项目(黔科合[2016]支撑2851);贵阳市科技计划项目(筑科合同[20161001]41号);贵州省普通高等学校科技拔尖人才支持计划(黔教合KY字[2017]072)

摘　　要：报道一种从L-乳酸出发拆分制备巴尼地平关键中间体(R)-1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-5-甲氧羰基-3-吡啶羧酸的合成新方法,即以L-乳酸为起始原料,经硫酸催化异丙酯化、2,2,6-三甲基-4H-1,3-二噁英-4-酮乙酰乙酰化后与3-氨基巴豆酸甲酯、间硝基苯甲醛进行Hantzsch反应,然后用乙醇重结晶拆分得到(S)-1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-5-甲氧羰基-3-吡啶羧酸-(S)-1-异丙氧基-1-氧代-2-丙醇酯,后者经碱水解、酸化得到目标产物,总收率20.6%,纯度98.66%,结构经1H NMR、HRMS鉴定。A novel method was reported for the resolution of(R)-2,6-dimethyl-4-(3-nitrophenyl)-5-(methoxycarbonyl)-1,4-dihydropyridine-3-carboxylic acid,the key intermediate of barnidipine.L-lactic acid was used as starting material via isopropylation,acetoacetylation,Hantzsch reaction and resolution to obtain(S)-3-((S)-1-isopropoxy-1-oxopropan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-5-(methoxycarbonyl)-1,4-dihydropyridine-3-carboxylate.Subsequently,the target product was obtained by hydrolysis and acidification with a total yield of 20.6%and a purity of 98.66%.The chemical structure was confirmed by 1H NMR and HRMS.

关 键 词：巴尼地平 关键中间体 L-乳酸 拆分 

分 类 号：R914[医药卫生—药物化学]