Urea intermediates as key gateways to 4-amino-1,5-dihydro-2H-chromeno[2,3-d]pyrimidin-2-one scaffolds: Synthetic streamlining and structural diversification

An efficient synthetic route to 4-amino-1,5-dihydro-2H-chromeno[2,3- d ]pyrimidin-2-one derivatives selectively functionalized at positions 5, 7, and 8 is presented. This method broadens the classical multi-fused heterocyclic synthesis of 2-amino-4H-chromene-3-carbonitriles by incorporating both aliphatic and aromatic aldehydes. A key feature is the two-step sequence involving acylation with benzoyl isocyanate to generate a urea intermediate, followed by intramolecular cyclization under basic conditions, enabling streamlined access to the tricyclic scaffold. The resulting chromene–cytosine hybrids broaden the structural diversity of cytosine analogs and constitute promising scaffolds for structure–activity relationship studies, with potential applications in oncology, infectious diseases, and epigenetic modulation. • Constructed novel chromene–cytosine hybrids via established methods combining privileged chromene and cytosine scaffolds. • Achieved regioselective chromene functionalization tolerant to diverse aldehydes, overcoming challenges in heterocyclic synthesis. • Used benzoyl isocyanate-mediated cyclization to suppress side reactions and achieve efficient ring closure to heterocyclic frameworks. • Expanded cytosine analog diversity via chromene–cytosine hybrids, offering versatile scaffolds for SAR and medicinal chemistry studies.