Molecular Hybridization-Guided Design and Synthesis of Novel Pyrazolylidene–Thiazolopyrimidine Derivatives

Abstract

Abstract The development of hybrid heterocyclic scaffolds represents an effective strategy for expanding the structural diversity of heterocyclic compounds. Herein, we report the synthesis of a new series of pyrazolylidene–thiazolopyrimidine hybrids through a concise and efficient synthetic route. The methodology involves the preparation of a diketopyrazolinone intermediate from dehydroacetic acid, followed by cyclocondensation with substituted 1,3,4-thiadiazol-2-amines or benzothiazol-2-amine in n-butanol under mild acidic conditions. The synthesized compounds were isolated in satisfactory yields (45–70%) and their structures were confirmed by 1H and 13C NMR spectroscopy and mass spectrometry. A plausible cyclocondensation mechanism is proposed to account for the formation of the fused heterocyclic products. The reported synthetic protocol provides convenient access to a novel class of pyrazolylidene–thiazolopyrimidine hybrids that may constitute valuable scaffolds for future medicinal chemistry applications.