Process development of potassium channel opener, TCV-295, based on convenient ring formation of 2H-1,3-benzoxazine and selective N-oxidation of the pyridyl moiety

An efficient process for potassium channel opener, TCV-295, based on a nove l and convenient 4-(2-pyridyl)-2H-1,3-benzoxazine ring formation from o-hyd roxybenzoylpyridine by the NH4I/piperidine/2,2-dimethoxypropane system and the following selective pyridine-N-oxidation using dimethyldioxirane, has b een developed. Additionally, the combination reagent of ammonium halide and sec- or tert- amine conveniently converted o-hydroxyphenyl arylketones wit h several ketones (or benzaldehyde) to various novel 4-aryl-2H-1,3-benzoxaz ines. (C) 2001 Elsevier Science Ltd. All rights reserved.