4H‐pyrido[1,2‐a]pyrimidin‐4‐one and their derivatives are highly bioactive and multipurpose heterocyclic motifs, having application in drugs, natural products, agrochemical, material science, and organic synthesis. The C‐H functionalization of basic core structure of heterocycles have become indispensable tools that have continually increased the importance in the pharmaceutical industry for the synthesis of various useful heterocyclic molecules and their derivatives. In this review, we have provided a summary of various routes to synthesize 4H‐pyrido[1,2‐a]pyrimidin‐4‐one derivatives along with various derivatization methods such as via cross‐coupling, C‐H functionalization through arylation, alkenylation, sulfenylation, selenylation, phosphonation etc. taking into account the synthetic potentiality and significant influence of this scaffold in drug discovery.

A mild and eco-friendly visible-light-mediated regioselective C–H alkoxycarbonylation of imidazo­[1,2-a]­pyridine heterocycles using rose bengal as a photoredox catalyst at room temperature has been developed. Biologically important alkoxycarboxylated imidazo­[1,2-a]­pyridines at the C-3 position as well as coumarins and quinoxalin-2­(1H)-ones have been prepared. The present approach has the advantage of having a user- and eco-friendly catalyst, a carbonyl source, as well as extremely mild conditions for direct and regioselective C–H alkoxycarbonylation mediated by visible light as a green energy source.

Metal-catalyst-free, organic dye-catalyzed C3–H arylation of pyrido­[1,2-a]­pyrimidin-4-ones using visible light irradiation was developed under mild reaction conditions. This operationally simple and direct C–H functionalization approach effectively produced biologically significant C3 arylated pyrido­[1,2-a]­pyrimidin-4-one and thiazolo­[3,2-a]­pyrimidin-5-one derivatives, including medicinally important endothelial cell dysfunction inhibitor and anti-inflammatory agents in good to excellent yields with good functional group tolerance. The present photoinduced direct C3–H arylation approach was suitable for scale-up synthesis.

A lenient approach for regioselective C3−H chalcogenation and thiocyanation of 4H‐pyrido[1,2‐a] pyrimidin‐4‐ones is developed using visible light photocatalysis. This operationally straightforward method furnishes a broad array of C‐3, Ar−S/Ar−Se and ‐SCN functionalized derivatives in moderate to high yields. This protocol employs visible light as an environmentally friendly energy source, cost effective inorganic persulfate‐based oxidant and easily procurable dichalcogenides for regioselective C−H chalcogenation of the substrate at room temperature. Further, regioselective thiocyanation of 4H‐pyrido[1,2‐a] pyrimidin‐4‐ones was also developed. Mechanistic path for these transformations has been proposed based on light on/off and Stern‐Volmer studies as well as quantum yield calculations.

A mild and efficient synergistic approach for decarboxylative aroylation of 2-aryl-pyrido[1,2-a]pyrimidin-4ones having intrinsic directing group has been developed by merging of palladium catalysis and photoredox catalysis at [a] R.