Synthesis of 5-substituted imidazo[4,5-b]pyridinones by annelation of 4-amino-5-ethoxalyl-1H-imidazole derivatives with active methylene compounds

A new synthetic route to imidazo[4,5-b]pyridinones with a range of substituents at the 6-position has been developed. These compounds can be prepared in four steps from readily available 5-chloro-4-nitroimidazoles. The key step involves construction of the pyridine ring by annelation of 4-amino-5-ethoxalylimidazoles with active methylene compounds under dehydrating conditions or by acylation with substituted acetyl chlorides followed by spontaneous cyclisation. An exception is the reaction in which cyclisation of a phenylacetyl derivative occurs to give a seven-membered ring, forming an imidazo[4,5-b]azepinedione.