This study involves the synthesis of pyrano]2,3‐d[pyrimidine derivatives using the multi‐component reactions (MCRs) under ultrasonic, and nanocatalysis conditions. The reaction efficiency was increased and the reaction time was reduced by using a prepared catalyst accomplished with sonication synergetic effect. Furthermore, the increase in product yield can be due to the synergistic property between metals on the surface of the catalyst. This catalyst was found to be recoverable and highly stable under ultrasonic conditions. The use of trimetallic multi‐walled carbon nanotubes (MWCNTs) proved to be highly effective in synthesis of the pyrano[2,3‐d]pyrimidine derivatives. This is due to their active site, economical catalyst loading, easy workup, reusability, and green reaction conditions. Also, the synthesized products were achieved in excellent yields and short reaction times. Different methods were utilized to characterize the nanocatalyst such as; Fourier‐transform infrared spectroscopy (FT‐IR), X‐ray powder diffraction (XRD), field emission scanning electron microscope (FE‐SEM), energy‐dispersive X‐ray spectroscopy (EDS), thermogravimetric analysis (TGA), and the hot filtration method. The synthesized organic compounds were identified through analyses using the melting point, FT‐IR method, and hydrogen‐1 nuclear magnetic resonance (1H NMR).