Greener Synthesis of Novel 1,2,3,4‐Tetrahydropyrimidine Derivatives Using Ionic Liquid for Targeting <i>Plasmodium falciparum</i> DHFR

Abstract The efficient synthesis of 1,2,3,4‐tetrahydropyrimidine derivatives in N,N ‐Diisopropylethylammonium acetate (DIPEAc) ionic liquid demonstrates a notable advancement in sustainable chemistry. The use of DIPEAc as a greener solvent enabled a highly efficient Biginelli‐type reaction, significantly reducing the environmental impact by eliminating the need for hazardous organic solvents. Our extensive screening and computational studies have identified these compounds as potential Plasmodium falciparum dihydrofolate reductase ( Pf ‐DHFR) inhibitors. The favorable ADME descriptors, suggesting promising pharmacokinetics, and the robust 3D‐QSAR model reveal strong structure–activity relationships, instilling confidence in the potential of these compounds for developing effective antimalarial treatments.