Synthesis and Reactions of 3‐Amino‐5,6‐Dimethyl‐l,2,4‐Triazine: DFT Studies, ADME Assay, and Molecular Docking on the new l,2,4‐Triazine Derivatives as Anticancer Agents.

Abstract Two effective one‐pot synthesis procedures were proposed for the synthesis of 3‐amino‐5,6‐dimethyl‐l,2,4‐triazine under free solvent conditions; these methods included fusing the monohydrazide of biacetyl with either methyl carbamimidothioate (Method B) or cyanamide (Method C). Simple reaction conditions, an easy work‐up process, and facile separation characterize the ecologically friendly fusion process used in techniques B and C. The results from methods B and C indicated the existence of amino‐imino prototropic tautomerism. The triazine in method C had a different melting point and had unusual mass spectral behavior, suggesting that it was in the imino‐tautomer form, as opposed to the amino‐tautomer form discovered in procedure B. The strong electron‐withdrawing activity of the triazine ring appears to deactivate the 3‐amino group, which in turn triggers the production of additional triazine derivatives ( 3 – 12 ), with yields ranging from 54% to 82%. To characterize the structure of the newly synthesized compounds, 1 H, 13 C‐NMR, and mass spectrometry were employed. The compounds that were created underwent testing at the National Cancer Institute. According to the screening results, conjugates 9 and 10 were successful against most of the cancer cell line subpanels. With the use of DFT, we conducted theoretical studies on compounds 9 and 10 . Topological studies, including ELF, LOL, and RDG, were used to identify the main binding sites and weak interactions of the target derivatives. The synthesized compounds that have promising properties are subjected to a pharmacological examination using Swiss‐ADME. Cox‐1 (PDB ID: 3KK6) is the target of molecular docking experiments that aim to identify the anticancer active site of the derivatives of interest.