Introduction: Pyrimidopyrimidines are one of the most important heterocyclic compounds with biological activities. Considering the aromatic structure of this compound, the non-bonding electron pair on the nitrogen atom, and its ability to form ligands and hydrogen bonds, this class of heterocyclic compounds exhibit high reactivity and has a wide range of applications. [1] Some biological properties of pyrimidopyrimidines can be mentioned as antioxidant, antiaggeration [2] , antiviral and anticancer [3] properties. Method: The reaction of ethoxymethylenemalononitrile (1) with methyl thiourea (2) in ethanol in the presence of diisopropylethylamine results in the formation of the corresponding pyrimidine (3) through cyclization involving the deprotonation of the amino moiety of thiourea. Subsequently, an appropriate aromatic carboxylic acid is treated with pyrimidine (3) in refluxing phosphorous oxychloride leading to the formation of the relative amide. The resulting amide undergoes a Pinner cyclization followed by a Dimroth rearrangement to afford the corresponding derivatives (4a-j). Results and discussion: In this research, novel derivatives of the heterocyclic system pyrimido[4,5-d]pyrimidine were synthesized. One of the most important advantages of this work is the high yields and purity of the products, as well as the simplicity of preparation of both starting materials and the final product. Furthermore, considering the symmetrical structure of pyrimido[4,5-d]pyrimidine derivatives, the newly synthesized heterocyclic derivatives can be exploited in new pharmaceutical, biochemical activity, and catalytic fields. References: ‏[1]S.Sahrapeyma, F.Shirini and M.Mamaghani. \\\"One-pot synthesis of pyrimido [4, 5-d] pyrimidine derivatives using a new DABCO-based ionic liquid catalyst.\\\" Iranian Journal of Catalysis 14.3 ,2024 [2] Ghada Ben, A., Maalej, E., Martin, H., Jacquinot, A. S., Barbanneau, N., Bernard, P. J., & Ismaili, L. (2024). Efficient Two-Step Synthesis of Novel Pyrimido [4, 5-d] Pyrimidines with Potent Neuroprotective, Antioxidant, and Aβ Anti-Aggregation Properties.‏ [3] Georgiou, E. A., Paraskevas, K., Koutra, C., Persoons, L., Schols, D., De Jonghe, S., & Kostakis, I. K. (2024). Exploring 4, 7-Disubstituted Pyrimido [4, 5-d] pyrimidines as Antiviral and Anticancer Agents. Molecules, 29(23), 5549.‏

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