Organocatalytic [3+2] Cycloaddition Reaction: Synthesis of Fully Decorated Sulfonyl 1,2,3‐Triazoles as Potent EGFR Targeting Anticancer Agents**

Abstract A general strategy was developed for the synthesis of new fully decorated sulfonyl1,2,3‐triazolyl imidazoles from β ‐ketosulfones and several aryl sulfonyl azides using the ramachary organocatalytic cycloaddition method. Organocatalytic [3+2] cycloaddition reaction of β ‐ketosulfone acts as an internal alkyne, as reported for the synthesis of sulfonyl‐1,2,3‐triazolyl imidazoles at 80 °C in good to excellent yields of products in the presence of catalytic amounts of pyrrolidine (10 mol %). In vitro anticancer activity of all these derivatives revealed that four compounds like 4‐((5‐(4‐methoxyphenyl)‐4‐((1‐methyl‐1 H ‐imidazol‐2‐yl) sulfonyl)‐1 H ‐1,2,3‐triazol‐1‐yl)sulfonyl) benzonitrile, 5‐(4‐methoxyphenyl)‐4‐((1‐methyl‐1 H ‐imidazol‐2‐yl)sulfonyl)‐1‐((4‐nitro phenyl) sulfonyl)‐1 H ‐1,2,3‐triazole,4‐((4‐((1‐methyl‐1 H ‐imidazol‐2‐yl) sulfonyl)‐5‐(4‐nitrophenyl)‐1 H ‐1,2,3‐triazol‐1‐yl)sulfonyl)benzonitrile, and 1‐((4‐chlorophenyl)sulfonyl)‐4‐((1‐methyl‐1 H ‐imidazol‐2‐yl) sulfonyl)‐5‐(4‐nitrophenyl)‐1 H ‐1,2,3‐triazole was active against three human cancer cell lines: MCF‐7, MDA‐MB‐231, and A‐549. Later, the results of the inhibitory assay of potent compounds against the tyrosine kinase epidermal growth factor receptor revealed that compounds 1‐((4‐chlorophenyl)sulfonyl)‐5‐(4‐methoxyphenyl)‐4‐((1‐methyl‐1H‐imidazol‐2‐yl)sulfonyl)‐1H‐1,2,3‐triazole and 1‐((4‐chlorophenyl) sulfonyl)‐4‐((1‐methyl‐1H‐imidazol‐2‐yl) sulfonyl)‐5‐(4‐nitrophenyl)‐1H‐1,2,3‐triazole showed more potency than the reference drug erlotinib.