【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).更多还原

【Abstract】 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-1,3-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]ethylamino}-2,4-(1 H,3 H)pyrimidinedione hydrochloride(Nifekalant hydrochloride)(1) in overall yield of about 54.5%(based on β-phenylpropanoic acid).更多还原