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In the current work, a convenient and simple approach for preparing poly (acrylic acid)/Fe3O4 supported on MIL-100(Cr) for the synthesis of pyrido [2,3-d]pyrimidine derivatives via the three-component one-pot reaction of 1,3-indandione, 6-amino uracil, and aromatic aldehydes is reported. The effectiveness of this new magnetic nanocatalyst was proved. The results showed this nanocatalyst's moderate to high yield under reflux conditions. SEM, TEM, IR, EDX, XRD, BET, and TGA were used to characterize the structure of the synthesized nanocatalyst. This synthetic protocol offers various advantages, including cost-saving, excellent yields in short reaction times (67–98%), low catalyst loading, and catalyst reusability.