An environmentally benign multi-component reaction: regioselective synthesis of fluorinated 2-aminopyridines using diverse properties of the nitro group

An efficient and concise one-pot procedure was developed for the synthesis of two kinds of fluorinated 2-aminopyridine compounds, 4 and 5, based on the reactions of different types of 1,1-enediamines (EDAMs), 1, with a variety of benzaldehyde derivatives, 2, and 1,3-dicarbonyl compounds, 3, involving the Knoevenagel, Michael and cyclization reactions under heating. This protocol is especially suitable for efficient and rapid parallel synthesis of fluorinated 2-aminopyridine compounds with pharmacological activity. The usefulness of this environmentally benign, mild, and multicomponent one-pot reaction procedure was demonstrated by easily synthesizing two kinds of fluorinated 2-aminopyridine libraries.