New method for the synthesis of diversely functionalized imidazoles from N-acylated alpha-aminonitriles.
[reaction: see text] A new general method for the synthesis of medicinally important diversely functionalized imidazoles from N-acylated alpha-aminonitriles has been developed. N-Acylated alpha-aminonitriles were reacted with triphenylphosphine and carbon tetrahalide to afford 2,4-disubstituted 5-halo-1H-imidazoles in good yield. This new methodology was applied for the synthesis of 2-butyl-4-chloro-5-hydroxymethylimidazole. These halo-imidazoles can be directly converted to 2,4,5-trisubstituted imidazoles through palladium-catalyzed coupling reactions.
Zhong
Yong-Li
YL
Department of Process Research, Merck Research Laboratories, P. O. Box 2000, Rahway, New Jersey 07065, USA. yongli_zhong@merck.com
Lee
Jaemoon
J
Reamer
Robert A
RA
Askin
David
D