肿瘤血管阻断剂vadimezan的合成

Synthesis of Tumor Vascular Disrupting Agent Vadimezan

2,3-二甲基苯胺与水合氯醛、盐酸羟胺经缩合反应生成2,3-二甲基异亚硝基乙酰苯胺,经脱水环合、开环及重氮化水解得2-羟基-3,4-二甲基苯甲酸,再与邻氯苯乙酸醚化和分子内付-克酰化反应制得肿瘤血管阻断剂vadimezan,总收率为40%。

Vadimezan,a vascular disrupting agent,was synthesized from 2,3-dimethylaniline by condensation with chloral hydrate and hydroxylamine hydrochloride to give 2,3-dimethyl-a-isonitrosoacetanilide,which was subjected to cyclization and ring opening to give 2-amino-3,4-dimethylbenzoic acid,followed by diazotization and hydrolysis,etherification with 2-chlorophenylacetic acid,and then Friedel-Crafts reaction with an overall yield of about 40%.