摘要
3-羟基丙腈与双乙烯酮反应后与间硝基苯甲醛和3-氨基巴豆酸甲酯经"一锅煮"反应制得中间体2,6-二甲基-4-(间硝基苯基)-1,4-二氢吡啶-5-羧酸甲酯-3-羧酸(4);4用奎尼丁拆分得(R)-4;(R)-4与(S)-N-苄基-3-羟基吡咯烷经酯化和成盐反应合成了盐酸巴尼地平,总收率12.7%,其结构经1H NMR,IR和ESI-MS确证。
A key intermediate, 2,6-dimethyl-4-（ m-nitrophenyl ）-1,4-dihydropyridine-3-carboxylic acid-5-carboxylate（4）, was prepared by reaction of 3-hydroxy-propionitril with diketene, then reacted with m-nitrobenzaldehyde and methyl 3-aminocrotonate. （R） -4 was obtained by resolution of 4 using quinidine as the resolution agent. Barnidipine hydrochloride in total yield of 12.7% was synthesized by esterifieation of （R）-4 with （S）-N-benzyl-3-hydroxy-pyrrolidine, then salifying. The structure was confirmed by 1H NMR, IR and ESI-MS.
出处
《合成化学》
CAS
CSCD
2015年第7期653-656,共4页
Chinese Journal of Synthetic Chemistry
关键词
盐酸巴尼地平
1
4-二氢吡啶
药物合成
工艺改进
Bamidipine hydrochloride
1,4-dihydropyridine
drug synthesis
process improvement
