Pyrrolo-imidazo[1,2‑a]pyridine Scaffolds through a Sequential Coupling of N‑Tosylhydrazones with Imidazopyridines and Reductive Cadogan Annulation, Synthetic Scope, and Application

A new strategy for the construction of 3-phenyl-1H-pyrrolo-imidazo­[1,2-a]­pyridine backbone is described. The reaction starts from the coupling between N-tosylhydrazones and 2-chloro-3-nitroimidazo­[1,2-a]­pyridines leading to the formation of 3-nitro-2-(arylvinyl)­imidazo­[1,2-a]­pyridine derivatives. Optimization of Cadogan-reductive conditions allowed the conversion of the obtained nitro derivative to a new scaffold of the type 3-aryl-1H-pyrrolo-imidazo­[1,2-a]­pyridine. This method provides rapid access to new libraries in the context of diversity-oriented synthesis, which intends to generate small molecules with a large structure diversity in an efficient manner. Screening of the biological activity of the newly generated compounds leads to the identification of a new promising compound 5cc, which exhibits good antiproliferative activity in the submicromolar range against a human colon cancer cell line.