A new strategy for synthesizing chirally enriched pyrazolylpyrimidinone-based glycohybrids has been achieved, employing an annulation approach in ethanol without any additives or catalysts under microwave conditions. The designed compounds were obtained within a short reaction time (5 min). This method offers several advantages, including mild reaction conditions, a green solvent, and a metal-free approach. Furthermore, the protocol demonstrated a broad substrate scope, successfully incorporating various functional groups with stereochemical diversity and furnishing chirally enriched molecules.