Convenient two-step synthesis of highly functionalized benzo-fused 1,4-diazepin-3-ones and 1,5-diazocin-4-ones by sequential Ugi and intramolecular SNAr reactions

Authors: Vézina-Dawod, Simon; Gerber, Nicolas; Liang, XinxiaBiron, Éric
Abstract: Benzodiazepinones are an important family of heterocycles with very attractive pharmacological properties and peptidomimetic abilities. We report herein a rapid and efficient two-step synthesis of polysubstituted 1,4-benzodiazepin-3-ones and 1,5-benzodiazocin-4-ones using a multicomponent condensation/cyclization strategy. The approach uses an Ugi four-component reaction to condense readily available Nα -Fmoc-amino acids, amines and isocyanides with a 2- fluorobenzaldehyde derivative followed by a one-pot Fmoc-group removal, intramolecular aromatic nucleophilic substitution for ring closure and side chain deprotection. The described method gives access to benzo-fused 7- and 8-membered rings bearing a wide variety of functionalized substituents and was applied to efficiently prepare tri- and tetrasubstituted 1,4- benzodiazepin-3-ones and 1,5-benzodiazocin-4-ones in high yields in two straightforward steps.
Document Type: Article de recherche
Issue Date: 18 September 2017
Open Access Date: 18 September 2019
Document version: AM
Permalink: http://hdl.handle.net/20.500.11794/15621
This document was published in: Tetrahedron, Vol. 73 (44),6347-6355 (2017)
https://doi.org/10.1016/j.tet.2017.09.028
Pergamon Press
Alternative version: 10.1016/j.tet.2017.09.028
Collection:Articles publiés dans des revues avec comité de lecture

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