The Box–Behnken experimental design has been applied to establish the optimized conditions for the synthesis of 2-amino-4,5-dihydro-5-oxo-4-phenylpyrano[3,2-c]chromene-3-carbonitrile over ZnO nano-particles as catalyst. ZnO nano-particles were prepared using the homogeneous precipitation method and 2-amino ethanol as precipitating agent. Three factors, three level Box–Behnken response surface design has been investigated using process parameters such as catalyst (0.05–0.5 mmol), solvent (5–20 mL) and temperature (50–90 °C). The results of the experiments were fitted to two quadratic polynomial models developed using response surface methodology, representing the functional relationship between the time and the yield of products and the experimental parameters. The predicted time and yield for optimal condition is 3.2 h and 94.6 %, respectively.