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.

Key words

imidazo-pyridine - Suzuki–Miyaura borylation reaction - NCI-60 cancer cell-line study - H₃₇Rv receptor based Mtb assays - regioselectivity

Publikationsverlauf

Eingereicht: 08. November 2022

Angenommen nach Revision: 12. Dezember 2022

Artikel online veröffentlicht:
25. Januar 2023

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