Pot, atom and step economic (PASE) assembly of salicylaldehydes, malononitrile dimer and 4-hydroxypyridine-2(1 H )-ones into medicinally relevant 5 H -chromeno[2,3- b ]pyridine scaffold

The new multicomponent reaction (MCR) has been found: one-pot selective and efficient formation of the new 5-(4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl)-substituted 5H-chromeno[2,3-b]pyridines in 61–97% yields directly from simple and easily available salicylaldehydes, malononitrile dimer and 4-hydroxypyridine-2(1H)-ones in small amount of pyridine–ethanol catalyst/solvent system. This complex “domino” transformation includes Knoevenagel condensation of salicylaldehyde with malononitrile dimer, Michael addition of 4-hydroxypyridine-2(1H)-one, double Pinner-type reaction cyclization and isomerization with following protonation. This facile multicomponent process opens a new way to 5-(4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl)-substituted 5H-chromeno[2,3-b]pyridine systems, which are promising compounds for the treatment for human inflammatory TNFα-mediated diseases and different biomedical applications.