Synthesis of Pyrido[2,3-d]pyrimidin-4(3H)-ones via SNAr/Tandem Cyclization

A new method has been developed for constructing the pyrido[2,3-d]pyrimidin-4(3H)-one scaffold under metal- and ligand-free conditions. In this strategy, 2-bromo-N-phenylnicotinamide is activated by the synergistic electron-withdrawing effects of the pyridine ring and the amide group, enabling tandem nucleophilic aromatic substitution (SNAr)/cyclization with cyanamide or formamide under simple conditions. Control experiments and density functional theory (DFT) calculations support an SNAr/cyclization mechanism. Preliminary photophysical studies show that the products exhibit blue emission, suggesting potential applications in materials science. Additionally, molecular docking studies indicate that the synthesized scaffold may have relevance to medicinal chemistry, providing a foundation for future biological evaluations.