Oxidative Cyclization Approach to Benzimidazole Libraries
2019-12-30T14:34:08Z (GMT) by
An efficient approach to the parallel synthesis of benzimidazoles from anilines is described. Library approaches to vary the N1 and C2 vectors of benzimidazoles are well established; however, C4–C7 variation has traditionally relied on 1,2-dianiline building blocks, providing limited chemical space coverage. We have developed an amidine formation/oxidative cyclization sequence that enables anilines as a diversity set for benzimidazole C4–C7 SAR generation in parallel format. The amidine annulation was achieved using PIDA or Cu-mediated oxidation to access both N–H and N–alkyl benzimidazoles. This library protocol has now been utilized for analog production in four medicinal chemistry projects. Additionally, the synthesis of aza-benzimidazoles from aminopyridines was achieved via an analogous sequence.
CC BY-NC 4.0