This paper describes the development, optimisation and exemplification of a copper-catalysed C–H functionalisation to form pharmaceutically relevant 2-aminobenzimidazoles from aryl-guanidines. High throughput screening was used as a tool to identify a catalytically active copper source, DoE was used for reaction optimisation and a range of aryl-guanidines were prepared and exposed to the optimum conditions to afford a range of 2-aminobenzimidazoles in moderate to good yields. The methodology has been applied to the synthesis of Emedastine, a marketed anti-histamine pharmaceutical compound, with the key cyclisation step performed on a gram-scale.
- copper-catalysed C–H functionalisation
Clark, P. R., Williams, G. D., & Tomkinson, N. C. O. (2019). Copper-catalysed C-H functionalisation gives access to 2-aminobenzimidazoles. Organic and Biomolecular Chemistry, 17(34), 7943-7955. https://doi.org/10.1039/C9OB01651A