Green Synthesis of Imidazo[1,2-a]pyridine–Chromone Hybrids via the Groebke–Blackburn–Bienaymé Reaction

Multicomponent reactions (MCRs) are powerful synthetic tools that enable the rapid and efficient synthesis of structurally diverse and complex molecular libraries in a single step, offering high atom economy and a greener alternative to conventional synthetic methodologies. Their operational simplicity, excellent functional group tolerance, and ability to combine three or more building blocks in a one-pot process make MCRs an important option for generating compound libraries in medicinal chemistry and drug discovery. Among these, the Groebke–Blackburn–Bienaymé reaction (GBB reaction) has emerged as one of the most versatile and widely used methods for the synthesis of imidazo[1,2-a]pyridines (IMPs), typically affording the products in high yields under mild reaction conditions. IMPs are recognized as privileged scaffolds in medicinal chemistry. Several marketed drugs, including Zolpidem, Olprinone, and Minodronic acid, incorporate the imidazo[1,2-a]pyridine core. Moreover, many IMP derivatives have been reported to exhibit a wide range of biological activities, including tubulin inhibition, PI3K inhibition, and antimycobacterial activity, highlighting the versatility of this heterocyclic framework for the development of new therapeutic agents. In the present work, we report the synthesis of a series of IMP analogs functionalized with a chromone moiety. The incorporation of this fluorophore imparts fluorescence to the compounds, as chromone derivatives are well known for their favorable photophysical properties. Consequently, these hybrid molecules are promising candidates for the development of fluorescent probes and functional materials with potential applications in chemical sensing and bioimaging.