Synthesis of Imidazo[1,2-a]pyridines via Multicomponent GBBR Using α-isocyanoacetamides

Abstract

Six novel imidazo[1,2-a]pyridines were synthesized by Groebke–Blackburn–Bienaymé reactions (GBBRs) under eco-friendly conditions (10 mol% ammonium chloride catalyst in EtOH at room temperature) with moderate to good yields (76–44%) using 2-isocyano-1-morpholino-3-phenylpropan-1-one. This is the first successful use of this type of α-isocyanoacetamide in a GBBR, as these reactive isonitriles readily undergo ring-chain tautomerization, as reported in other IMCRs (isonitrile-based multicomponent reactions). The product structures contain a peptidomimetic imidazo[1,2-a]pyridine scaffold linked to an α-aminomorpholide and are of interest to medicinal chemists.

Recent Advances in the Synthesis of Imidazo[1,2‐a]pyridines: A Brief Review

“…The GBBR is one of the most common and efficient strategies to synthesize imidazole scaffolds [88] . Hence, to develop green conditions for the GBBR, Gómez et al [89] . in 2019 reported a green synthesis of imidazo[1,2‐ a ]pyridines 99 by eco‐friendly method via multicomponent GBBR using 2‐isocyano‐1‐morpholino‐3‐phenylpropan‐1‐one 98 , aldehydes 97 and 2‐aminopyridine 12 in good to excellent yields.…”