Ultrasound-assisted, mild and highly efficient route for the one-pot multicomponent reaction of ethyl acetoacetate, hydrazine hydrate, aromatic aldehydes and barbituric acid has been developed for the construction of bioactive heterocyclic moieties in a single molecular framework. The synthesis of tri-heterocyclic fused pyrazolopyranopyrimidines promoted by beta-Cyclodextrin as a biomimetic catalyst and water as an eco-friendly reaction medium. This environmentally beningn protocol offers selective synthesis of pyrazolopyranopyrimidine derivatives without any side product with excellent yield in shorter duration. The reusability and recyclability of catalyst is carried out in simple way. Also, this method provides various advantages such as metal free synthesis, cost-effective catalyst, no column chromatography and offers easy isolation of products with gram scale synthesis. Graphic