A mild method for the formation and in situ reaction of imidoyl chlorides: conversion of pyridine-1-oxides to 2-aminopyridine amides.
[reaction: see text] A mild, practical, one-pot method for the generation of imidoyl chlorides and their subsequent in situ reaction with pyridine-1-oxides is described. The imidoyl chlorides were formed from the reaction of secondary amides with a stoichiometric amount of oxalyl chloride and 2,6-lutidine in CH(2)Cl(2) at 0 degrees C. Upon warming of the reaction mixture to room temperature in the presence of pyridine-1-oxides, a rapid conversion to 2-aminopyridine amides was observed in moderate to excellent isolated yields.
Manley
Peter J
PJ
Department of Medicinal Chemistry, Merck & Co., Inc., P.O. Box 4, West Point, Pennsylvania 19486, USA.
Bilodeau
Mark T
MT
D000577:Amides / Q000138:chemical synthesis*; D000631:Aminopyridines / Q000138:chemical synthesis*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002712:Chlorides / Q000737:chemistry; D010070:Oxalates / Q000737:chemistry; D010087:Oxides / Q000737:chemistry
D000577:Amides; D000631:Aminopyridines; D002712:Chlorides; D010070:Oxalates; D010087:Oxides; C092266:oxalyl chloride; C032439:alpha-aminopyridine