血管阻断剂(Z)-2-甲氧基-5-[2-(3,4,5-三甲氧基苯基)乙烯基]-苯胺的合成  

Synthesis of Vascular Disrupting Agent(Z)-2-Methoxy-5[2-(3,4,5-trimethoxyphenyl)vinyl]-phenylamine

作　　者：甄永刚[1] 邹永[1] 

机构地区：[1]中国科学院广州化学研究所

出　　处：《精细化工》2007年第4期372-375,共4页Fine Chemicals

基　　金：广东省科技计划项目(2006B35604002);广东省自然科学基金项目(04002264)

摘　　要：对(Z)-2-甲氧基-5-[2-(3,4,5-三甲氧基苯基)乙烯基]-苯胺(AVE-8063)的合成进行了研究。采用两条路线得到AVE-8063,均以对甲氧基苯乙酸为起始原料,经硝化、Perk in缩合、还原得到(E)-2-(3-氨基-4-甲氧基苯基)-3-(3,4,5-三甲氧基苯基)-丙烯酸(Ⅳ),直接脱羧得到目标化合物(路线1);为改善后处理操作条件,还将化合物Ⅳ的氨基保护、再经脱羧及去保护得到目标化合物(路线2)。路线1和路线2的总收率分别为20.4%和17.1%,均高于文献报道的W ittig反应路线,各中间体及产物结构经MS、IR以及1HNMR确证。New synthetic routes for （ Z ）-2-methoxy-5-[ 2-（ 3, 4, 5-trimethoxyphenyl ） vinyl ]- phenylamine were devised. Starting from 4-methoxyphenylacetic acid, through nitration, Perkin condensation and reduction, （E） -2- （3-amino-4-methoxyphenyl） -3- （ 3,4,5- trimethoxyphenyl ） -acrylic acid was obtained, which by direct decarboxylation （route 1 ）, or with a more favourable procedure through N-acetyl protection, decarboxylation and hydrolyzation （ route 2 ）, gave the target compound. The total yields of route 1 and route 2 were 20. 4% and 17. 1% respectively, both higher than Wittig method. The structure of the target compound and key intermediates were verified by MS, IR and ^1HNMR.

关 键 词：AVE-8063 PERKIN反应 血管阻断剂 

分 类 号：R914.5[医药卫生—药物化学]