A facile synthesis of tetracyclic benzo-pyridonaphthyridines by domino reaction

A novel methodology for the synthesis of tetracyclic benzo-pyridonaphthyridines, forming a C–C and a C–N bond in concentrated sulfuric acid at 70 °C in a one-pot is reported. The key substrates (9a–m) are prepared by reacting 2-chloro-6-(4-fluorophenyl)-4-methylnicotinenitrile (7) with various anilines followed by dimethylformamide dimethylacetal. The domino reaction is initiated by the protonation of the β-carbon of the enamine group in 9a–m and terminated by the elimination of dimethylamine.