Regioselective Pd-Catalyzed Suzuki–Miyaura Borylation Reaction for the Dimerization Product of 6-Bromoimidazo[1,2-a]pyridine-2-carboxylate: Mechanistic Pathway, Cytotoxic and Tubercular Studies

Abstract

In the pharmaceutical industry, boronic acid and esters play an important role in API-based synthesis. The most efficient way of preparing various active agents is palladium-catalyzed Suzuki–Miyaura borylation reactions. Herein, we report the formation of dimerization product [6,6′-biimidazo[1,2-a]pyridine]-2,2′-dicarboxamide derivatives 7a–j from 6-bromoimidazo[1,2-a]pyridine-2-carboxylate by employing the same conditions. A regioselective borylation of ethyl 6-bromoimidazo[1,2-a]pyridine-2-carboxylate (3) was examined for the formation of ethyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine-2-carboxylate (4a) but it was found to be directed towards the dimerization product 5. The nitrogen-rich system was incorporated into potential anti-cancer and anti-TB agents through acid amine coupling reactions between acid 6 and various amines (dialkyl/cyclic sec./tert.) to form the final adducts 7. Five derived scaffolds were identified as moderately active in TB activity against the H37Rv strain, while two compounds were found to be particularly potent in NCI-60 anti-cancer screening in nine cancer panels.