摘要
以2-甲硫基嘧啶-4-(3-氯-4-甲氧基苄基)-氨基-5-羧酸乙酯和80%过氧化氢异丙苯进行氧化反应得到2-甲基亚砜嘧啶-4-(3-氯-4-甲氧基苄基)-氨基-5-羧酸乙酯(3);3与(R)-(-)-2-(羟甲基)吡咯烷缩合得到的2-[(R)-2-羟甲基吡咯烷基-1-]-4-(3-氯-4-甲氧基苄胺基)-5-嘧啶羧酸乙酯(3);3经氢氧化钠水解,酸化后得到2-[(R)-2-羟甲基吡咯烷基-1-]-4-(3-氯-4-甲氧基苄胺基)-5-嘧啶羧酸(7);7在N,N-二乙基乙酰胺中三乙胺催化下与2-氨基甲基嘧啶甲磺酸盐、1-乙基-(3-二甲基氨基丙基)碳二亚胺盐酸盐、1-羟基苯并三唑混合反应得到(R)-阿伐那非(1),总收率49.0%,并对合成物质进行结构表征确证。
Ethyl 2-methylsulfoxide-pyrimidin-4-(3-chloro-4-methoxybenzyl)-amino-5-carboxylate(■)was synthesized by oxidation of ethyl 2-methylthiopyrimidin-4-(3-chloro-4-methoxybenzyl)-amino-5-carboxylate using 80%cumene hydroperoxide;Ethyl 2-[(R)-2-hydroxymethylpyrrolidinyl-1-]-4-(3-chloro-4-methoxybenzylamino)-5-pyrimidine carboxylate(■)was synthesized by condensation of(R)-(-)-2-(hydroxymethyl)pyrrolidine with■;2-[(R)-2-hydroxymethylpyrrolidinyl-1-]-4-(3-chloro-4-methoxybenzylamino)-5-pyrimidine carboxylic acid ethyl ester(■)was obtained by hydrolysis of■with sodium hydroxide and acidification;Under the catalysis of triethylamine in N,N-diethylacetamide,(R)-avanafil(■)was synthesized by the mixed reaction with■,2-aminomethylpyrimidine methanesulfonate,1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 1-hydroxybenzotriazole in an overall yield of 49.0%.The structure of the synthesized substance was characterized.
作者
阳学文
杨硕
何军芳
吴兴
杨彩霞
张杨琳
韦晶晶
YANG Xue-wen;YANG Shuo;HE Jun-fang;WU Xing;YANG Cai-xia;ZHANG Yang-lin;WEI Jing-jing(Zhejiang Apeloatospo Pharmaceutical Co.,Ltd.,Dongyang 322118,China;Hengdian Group Holding Co.,Ltd.,Dongyang 322118,China;Zhejiang Apeloa Jiayuan Pharmaceutical Co.,Ltd.,Dongyang 322118,China)
出处
《精细化工中间体》
CAS
2021年第2期42-45,共4页
Fine Chemical Intermediates
