Preparation of N-alkylated pyridones via selective N-alkylation of 2-alkoxypyridines on solid phase

Regioselective solid-phase synthesis of N-alkylated 2-pyridones has been carried out starting from 2-halopyridines. Variously substituted 2-halopyridines were linked to a Wang resin in quantitative yields to afford 2-alkoxypyridines. The coupled products were then reacted with a variety of alkyl halides, resulting in tandem alkylation and cleavage from the resin to generate N-alkylated pyridones With no detectable traces of O-alkylated products. The scope and limitations of this exceptionally selective reaction have been studied.