Abstract Targeting cyclin-dependent kinases (CDKs) presents a promising approach to cancer therapy. Therefore, creating CDK inhibitors is crucial for effective cancer treatment. This study discloses the green synthesis of nine pyrido[2,3-d]pyrimidines derivatives 6–14 as CDK1 inhibitors by applying TiO2 nanoparticles as a catalyst. The structures of the reported compounds were verified using various techniques, including IR and NMR spectroscopy, as well as elemental analysis.