A novel flow-based approach for the preparation of benzimidazol-2-one (1) scaffold by the\n1,1â??-carbonyldiimidazole (CDI)-promoted cyclocarbonylation of o-phenylenediamine (2) is reported.\nStarting from a preliminary batch screening, the model reaction was successfully translated under\nflow conditions and optimised by means of design of experiment (DoE). The method allowed the\nefficient preparation of this privileged scaffold and to set up a general protocol for the multigram-scale\npreparation in high yield, purity, and productivity, and was successfully applied for the multigram flow\nsynthesis of N-(2-chlorobenzyl)-5-cyano-benzimidazol-2-one, which is a key synthon for hit-to-lead\nexplorations in our anti-inflammatory drug discovery program.
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