Enamination of 2- and 4-pyridones as a method for synthesis of 1,6-naphthyridones. π-π Stacking catalysis for heterocyclization

Abstract A novel method for the synthesis of 1,6-naphthyridones via enamination of 2- and 4-pyridones has been developed. The scalable and convenient strategy is based on carbamoylated enaminones and 2-pyridones prepared from bioprivileged triacetic acid lactone. Сarbamoylated enaminones undergo double enamination leading to 1,6-diaryl-1,6-naphthyridine-4,5(1H,6H)-diones in 10-64% yields (for two step). The enamination of 4-amino-2-pyridones with DMF-DMA proceeds at the C-3 position followed by electrocyclization for the construction of 2-arylbenzo[b][1,6]naphthyridin-1(2H)-ones (27–71% yields). A rare example of π-π stacking catalysis was discovered, where nicotinonitrile facilitates the heterocyclization reaction with DMF-DMA. The prepared 1,6-naphthyridones demonstrated perspective antitumor activity.