Palladium‐Catalyzed Regioselective Coupling of Amidines and 1,2,3‐Triiodobenzenes: Facile Synthesis of 2,3‐Diiodinated N‐Arylbenzimidamides as Potential MDM₂ and MDM₄ Inhibitors

Abstract

A facile and unprecedented synthesis of 2,3-diiodinated Narylbenzimidamide derivatives through highly regioselective Buchwald-Hartwig coupling of 5-substituted-1,2,3-triiodobenzene and amidine is described. Remarkably, the amination reactions are proceeded exclusively at the terminal positions, the less sterically hindered, and the most regioactive positions. The highest yields were isolated from a combination between electron-poor 1,2,3-triiodoarenes and electron-poor benzimidamides. The optimized conditions were found to be suitable for many functional groups. This report discloses the first method to make 2,3-diiodinated N-arylbenzimidamides that is efficient, general in scope, highly regioselective, and truly remarkable precursors for other transformations [a]

Applications of palladium-catalyzed C–N cross-coupling reactions in pharmaceutical compounds

“…Compound 117 was introduced as the most effective derivative as a potential compound for MDM2 and MDM4 activity-related disease therapy. 194 Its large-scale synthesis comprises two main steps C–N bond formation and ring-closing metathesis reaction.…”