Copper‐Catalyzed Domino S ‐Arylation/ N ‐Arylation for the Synthesis of Benzo4,5Thiazolo3,2‐ a Pyrimidin‐4‐ones and N ‐(Benzo d thiazol‐2‐yl)acetamides With Preliminary Anti‐Inflammatory Evaluation

ABSTRACT A regioselective copper‐catalyzed domino S ‐arylation/ N ‐arylation strategy has been developed for the efficient synthesis of 2‐hydroxy‐4 H ‐benzo4,5thiazolo3,2‐ a pyrimidin‐4‐ones 3 and N ‐(benzo d thiazol‐2‐yl)acetamides 4 from 1‐bromo‐2‐iodobenzenes and 6‐hydroxy‐2‐thioxo‐2,3‐dihydropyrimidin‐4(1 H )‐ones. The transformation proceeds smoothly in the presence of CuI as a catalyst and pivalic acid as an additive in DMSO, affording the desired products in good to excellent yields (66%–85%). Preliminary biological evaluation revealed notable in vivo anti‐inflammatory activity for several derivatives, with compounds 4d, 3a, and 3f exhibiting higher activity than the reference drug indomethacin while maintaining favorable safety profiles. Molecular docking studies further indicated strong binding affinity toward the COX‐2 active site, particularly for halogenated derivatives 3b–f , with compound 3f showing the lowest binding energy (−10.30 kcal/mol). These results highlight the potential of the synthesized scaffolds for further exploration as anti‐inflammatory agents.