A novel, multicomponent approach to 2-(imidazo[1,2-a]pyridin-3-yl)-N,N-dialkylacetamides (very important class of fused heterocyclic derivatives, known to act on central nervous system by enhancing the activity of the GABA) is reported. It is based on the carbonylation reaction of N-Boc-(prop-2-yn-1-yl)pyridin-2-amines carried out in the presence of secondary amines (2–3 equiv) under oxidative conditions, using oxygen (from air) as oxidant (4:1 CO-air, total pressure 20 atm) and PdI2/KI as the catalytic system (0.33–1 mol% of PdI2 and 0.5 equiv of KI) in MeCN as the solvent at 100 °C. The process leads to the target compounds in good to high yields (67–90%) through an ordered sequence of steps, occurring in situ under the reaction conditions: Boc-deprotection of the substrate is followed by PdI2/KI-catalyzed oxidative monoaminocarbonylation of the terminal triple bond (or vice versa) to give a 2-ynamide intermediate, which then undergoes intramolecular aza-Michael reaction and isomerization.

A multicomponent palladium-catalyzed carbonylative approach to imidazopyridinyl-N,N-dialkylacetamides

Veltri L.
;
Russo P.;Vitale P.;Gabriele B.
2020

Abstract

A novel, multicomponent approach to 2-(imidazo[1,2-a]pyridin-3-yl)-N,N-dialkylacetamides (very important class of fused heterocyclic derivatives, known to act on central nervous system by enhancing the activity of the GABA) is reported. It is based on the carbonylation reaction of N-Boc-(prop-2-yn-1-yl)pyridin-2-amines carried out in the presence of secondary amines (2–3 equiv) under oxidative conditions, using oxygen (from air) as oxidant (4:1 CO-air, total pressure 20 atm) and PdI2/KI as the catalytic system (0.33–1 mol% of PdI2 and 0.5 equiv of KI) in MeCN as the solvent at 100 °C. The process leads to the target compounds in good to high yields (67–90%) through an ordered sequence of steps, occurring in situ under the reaction conditions: Boc-deprotection of the substrate is followed by PdI2/KI-catalyzed oxidative monoaminocarbonylation of the terminal triple bond (or vice versa) to give a 2-ynamide intermediate, which then undergoes intramolecular aza-Michael reaction and isomerization.
Carbonylation
Fused heterocycles
Imidazopyridines
Multicomponent reaction
Palladium
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11770/305371
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