Selective, C-3 Friedel-Crafts acylation to generate functionally diverse, acetylated Imidazo[1,2-a]pyridine derivatives.

ABSTRACT: Carbon-carbon bonds are integral for pharmaceutical discovery and development. Frequently, C-C bond reactions utilize expensive catalyst/ligand combinations and/or are low yielding, which can increase time and expenditures in pharmaceutical development. To enhance C-C bond formation protocols, we developed a highly efficient, selective, and combinatorially applicable Friedel-Crafts acylation to acetylate the C-3 position of imidazo[1,2-a]pyridines. The reaction, catalyzed by aluminum chloride, is both cost effective and more combinatorial friendly compared to acetylation reactions requiring multiple, stoichiometric equivalents of AlCl3. The protocol has broad application in the construction of acetylated imidazo[1,2-a]pyridines with an extensive substrate scope. All starting materials are common and the reaction requires inexpensive, conventional heating methods for adaptation in any laboratory. Further, the synthesized compounds are predicted to possess GABA activity through a validated, GABA binding model. The developed method serves as a superior route to generate C-3 acetylated imidazo[1,2-a]pyridine building-blocks for combinatorial synthetic efforts.

SUBMITTER: Frett B 

PROVIDER: S-EPMC6192254 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature