An expeditious and highly efficient methodology for the synthesis of pyrazolopyranopyrimidine under aqueous conditions is reported using guanidine hydrochloride as a catalyst. One-pot multicomponent synthesis from aryl/heterocyclic aldehyde, ethyl acetoacetate, barbituric acid, and hydrazine hydrate to give the final compound in moderate to excellent yield. The recyclability (up to 4 cycles), safe, low cost, and wide stability profile of guanidine hydrochloride fulfil the ideal properties of the catalyst. The current protocol shows several advantages such as its environmentally benign nature, shorter reaction time, high yield, simple work-up procedure, broad substrate tolerance, absence of hazardous organic solvent, etc.