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, Xinxia; Biron, 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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