A practical synthesis of 6-[2-(2,5-dimethoxyphenyl)ethyl]-4-ethylquinazoline and the art of removing palladium from the products of Pd-catalyzed reactions

被引：95

作者：

Königsberger, K ^{[1
]}

Chen, GP ^{[1
]}

Wu, RR ^{[1
]}

Girgis, MJ ^{[1
]}

Prasad, K ^{[1
]}

Repic, O ^{[1
]}

Blacklock, TJ ^{[1
]}

机构：

[1] Novartis Biomed Res, Proc Res & Dev, E Hanover, NJ 07936 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2003年 / 7卷 / 05期

关键词：

D O I：

10.1021/op034072x

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A concise large-scale synthesis of 1, a new antimitotic agent is described. The key step was a one-pot Sonogashira cross-coupling of an aryl halide with a heteroaryl halide through an acetylene using the readily available 2-methyl-3-butyn-2-ol (7). An innovative approach for palladium removal was designed and successfully scaled-up on a multikilogram scale. The product was crystallized from the crude reaction mixture while keeping the residual palladium in the mother liquor by using Pd-scavenging agents such as N-acetylcysteine or thiourea.

引用

页码：733 / 742

页数：10

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