MCC/SNAr methodology. Part 1: Novel access to a range of heterocyclic cores

The novel solution-phase syntheses of arrays of biologically relevant indaz olinones. benzazepines and benzoxazepines, utilizing multi-component conden sation (MCC)/SNAr methodology is reported. Reaction of commercially availab le 2-fluoro-5-nitrobenzoic acid with an aldehyde, isonitrile and a primary amine tethered to a Boc-protected internal amino or hydroxyl nucleophile, a ffords the Ugi product in good yield. Subsequent acid treatment followed by proton scavenging promotes cyclization of internal amino nucleophiles to a variety of ring sizes. Base treatment alone is sufficient to generate benz oxazepines. Interestingly, this communication also introduces a highly effi cient two-step route to benzimidazoles. (C) 2001 Elsevier Science Ltd. All rights reserved.