Metal-Free Assembly of Four C-N and Two C-C Bonds: Diestereoselctive Synthesis of Pyrido [1,2-a] pyrimidines via a FiveComponent Reaction

A highly convergent heteroannulation protocol for the synthesis of N-fused, pyrido[1,2-a]pyrimidines was successfully achieved via a one-pot, sequential fivecomponentreaction, utilizing primary amines, diketene, differently substituted aromatic aldehydes, nitro ketene dithioacetal and propanediamine in ethanol at 70oC. This new efficient domino protocol generates two rings by the concomitant formation of C–N (four) and C–C (two) multiple bonds presumably via a sequential reaction involving, ring-opening/ Knoevenagel condensation, /nucleophilic substitution (SN)/ Michael addition followed by imine-enamine tautomerization and final N-cyclization. The merit of this protocol is highlighted by its easily available or readily accessible starting materials, operational simplicity, atom economy, clean reaction profile, and tolerance towards to a wide variety of functional groups. The products were isolated by just decantation of the solvent and for the purification column chromatography was non-required. Pyridopyrimidines, display a broad spectrum of pharmaceutical applications such as anti-inflammatory, antioxidant, anticancer, antimicrobial, and antiviral and constitutethe backbones of several prescribed drugs[1]. In this important line pyrido[1,2- a]pyrimidine structural unit is present in some prescribed and market purchasable drugs, such as the tranquilizer, pirenperone[2], antiasthmatic agent, pemirolast[3], barmastine, and antiulcerative agent.