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

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 de...

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Bibliographic Details
Published in:Organic process research & development 2003-09, Vol.7 (5), p.733-742
Main Authors: Königsberger, Kurt, Chen, Guang-Pei, Wu, Raeann R, Girgis, Michael J, Prasad, Kapa, Repič, Oljan, Blacklock, Thomas J
Format: Article
Language:English
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Summary: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.
ISSN:1083-6160
1520-586X
DOI:10.1021/op034072x