Introduction: Selenophenopyrimidines are heterocyclic compounds that have attracted considerable attention due to their unique chemical and pharmacological properties. The central core of selenophenopyrimidine has a stable and diverse structure, enabling the synthesis of various derivatives with different properties. These compounds show promise for pharmaceutical applications such as antitumor [1], antioxidant [2] and antimicrobial [3] activities. Method: This research describes an efficient multi step synthesis for novel 7-cyano-6-(pyrrolidin-1-yl)selenopheno[3,2-d]pyrimidine derivatives (4a-e). Initially, compound (1) was prepared according to our previous reports[4],[5]. Subsequent hydrolysis of compound (1) was converted to an amide, using concentrated sulfuric acid the carboxamide (2), followed by cyclization with carbon disulfide to furnish the core structure 7-cyano-4-oxo-6-(pyrrolidin-1-yl)-2-thioxo-1,2,3,4-tetrahydroselenopheno[3,2-d]pyrimidine (3). Finally, alkylation of this core scaffold led to a diverse array of dialkylated selenopheno[3,2-d]pyrimidine derivatives (4a-e) with potential applications, particularly in the pharmaceutical field. Results and discussion: This research synthesized novel derivatives of the selenophenopyrimidine. One of the most significant advantages of this synthetic approach is the simplicity of the procedures, high yields, and high purity of the products at each stage. One of the simplest synthetic steps involved the production of the final derivatives, which was achieved using the green solvent ethanol without the need for complex separation steps. Finally, a wide range of dialkyl derivatives was synthesized by reacting this compound with various alkyl halides. Ethanol instead of other toxic solvents is the advantage of this synthetic method, which is of great environmental importance and easy to use. References: [1] Kohandel O, Sheikhi-Mohammareh S, Oroojalian F, Memariani T, Mague J, Shiri A. A Dimroth rearrangement approach for the synthesis of selenopheno [2, 3-e][1, 2, 4] triazolo [1, 5-c] pyrimidines with cytotoxic activity on breast cancer cells. Molecular diversity. 2022 Jun;26(3):1621-33. [2] Farzamnezhad I, Sheikhi-Mohammareh S, Beyzaei H, Yarmohammadi E, Shiri A. Synthesis of Novel DPPH-Free Radical Scavenger Se-Containing Fused Chalcogenophenes: 2-Alkyl-7-Cyano-4-Imino-3-Phenyl-6-(pyrrolidin-1-yl)-3, 4-Dihydroselenopheno [3, 2-d] Pyrimidines. Polycyclic Aromatic Compounds. 2024 Feb 7;44(2):807-17. [3] Helal MH, Salem MA, Gouda MA. Recent advances in the Chemistry of Selenophenopyrimidine Heterocycles: Synthesis, Reactivity, and Biological Activity. Journal of Organometallic Chemistry. 2024 Aug 30:123343. [4] Yu SY, Cai YX. Synthesis of polysubstituted pyrimidines from ketene dithioacetals using KF/Al2O3 catalyst. Synthetic communications. 2003 Dec 1;33(22):3989-95. [5] Thomae D, Kirsch G, Seck P. Synthesis of selenophene analogues of the tacrine series: comparison of classical route and microwave irradiation. Synthesis. 2008 May;2008(10):1600-6.

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