co9b00189_si_001.pdf (2.09 MB)
Oxidative Cyclization Approach to Benzimidazole Libraries
journal contribution
posted on 2019-12-30, 14:34 authored by Eric P. Arnold, Prolay K. Mondal, Daniel C. SchmittAn 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.