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

Brendan Frett, Nicholas McConnell, Anupreet Kharbanda, Gunaganti Naresh, Benjamin Rounseville, Christina Warner, John Chang, Natalie Debolske, Hong Yu Li

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4592-4600
Number of pages9
JournalTetrahedron
Volume74
Issue number35
DOIs
StatePublished - Aug 30 2018
Externally publishedYes

Fingerprint

Acylation
Derivatives
gamma-Aminobutyric Acid
Carbon
Acetylation
Health Expenditures
Pharmaceutical Preparations
Heating
Ligands
Costs and Cost Analysis
Catalysts
Substrates
imidazo(1,2-a)pyridine
Costs
aluminum chloride

Keywords

  • Combinatorial chemistry
  • Drug discovery
  • Friedel-Crafts acylation
  • Imidazo[1,2-a]pyridine
  • Library generation

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

Selective, C-3 Friedel-Crafts acylation to generate functionally diverse, acetylated Imidazo[1,2-a]pyridine derivatives. / Frett, Brendan; McConnell, Nicholas; Kharbanda, Anupreet; Naresh, Gunaganti; Rounseville, Benjamin; Warner, Christina; Chang, John; Debolske, Natalie; Li, Hong Yu.

In: Tetrahedron, Vol. 74, No. 35, 30.08.2018, p. 4592-4600.

Research output: Contribution to journalArticle

Frett, B, McConnell, N, Kharbanda, A, Naresh, G, Rounseville, B, Warner, C, Chang, J, Debolske, N & Li, HY 2018, 'Selective, C-3 Friedel-Crafts acylation to generate functionally diverse, acetylated Imidazo[1,2-a]pyridine derivatives', Tetrahedron, vol. 74, no. 35, pp. 4592-4600. https://doi.org/10.1016/j.tet.2018.07.027
Frett, Brendan ; McConnell, Nicholas ; Kharbanda, Anupreet ; Naresh, Gunaganti ; Rounseville, Benjamin ; Warner, Christina ; Chang, John ; Debolske, Natalie ; Li, Hong Yu. / Selective, C-3 Friedel-Crafts acylation to generate functionally diverse, acetylated Imidazo[1,2-a]pyridine derivatives. In: Tetrahedron. 2018 ; Vol. 74, No. 35. pp. 4592-4600.
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