Cine substitution in reaction of unactivated 2-halopyridines with 2-aminopyridine 1-oxide. Formation of 3-(2-pyridylamino)-2(1H)-pyridone [1]

Reaction of 2-aminopyridine 1-oxide 1a with 2-fluoropyridine 5a in DMF at 140 degree C gave 2-(2-pyridylamino)pyridine 1-oxide 6 (41%) along with bis(2-pyridyl)amine 7 (5%). However, heating in melt of 1a with 2-chloropyridine 5b or 2-bromopyridine 5c in the presence of dry potassium carbonate at 175 degree C provided 3-(2-pyridylamino)-2(1H)-pyridone 9 as cine substitution product. Compound 9 results from the nucleophilic attack of the N-oxide on the carbon atom bearing halogen to give corresponding cation 17, which rearranges to cine substitution product 9 via anhydro-base 18.