摘要
以β-苯基丙酸为起始原料,依次经硝化、N-酰化和还原反应合成了盐酸尼非卡兰药物关键中间体——N-(2-羟乙基)-N-[3-(4-硝基苯基)]丙胺,三步总收率达66.5%.又以1,3-二甲基脲为原料,依次经氰基乙酸环合、乙醇胺脱胺、二氯亚砜氯化制得另一中间体——6-(2-氯乙基)氨基-1,3-二甲基-嘧啶二酮.上述二中间体反应形成1,3-二甲基-6-{2-[N-(2-羟乙基)-3-(4-硝基苯基)丙氨]乙氨基}-2,4-(1H,3H)-嘧啶二酮盐酸盐(盐酸尼非卡兰),总收率为54.5%(以β-苯基丙酸基准计算).
N- (2-Hydroxyethyl)-N- [3-(4-nitrophenyl)propyl] amine(3), the key intermediate for the synthesis of Nifekalant hydrochloride, was prepared from β- phenylpropanoic acid as starting material in three-step by reaction of nitration, N- acylation and reduction in overall yield of about 66.5%. Additionally, 6-(2-chloroethyl)amino-l, 3- dimethylpyrimidinedione(7), as another key intermediate, was synthesized by condensation of 1,3-dimethylurea successively with cyanoacetic acid and then treated with ethanolamine, followed by chlorination with thionyl chloride. Reaction of (3) with (7) afforded target compound 1,3-dimethyl-6-{2-[ N- (2-hydroxyethyl)-3-(4-nitrophenyl)propylamino] ethylaminol-2,4-( 1 H, 3 H )pyrimidinedione hydrochloride (Nifekalant hydrochloride)( 1 ) in overall yield of about 54.5 % (based on β -phenylpropanoic acid).
出处
《江西师范大学学报(自然科学版)》
CAS
北大核心
2007年第4期340-343,共4页
Journal of Jiangxi Normal University(Natural Science Edition)
基金
国家自然科学基金(205622005)
江西省教育厅科技项目(赣财教[2004]18号)资助