Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5211859 | Tetrahedron | 2017 | 9 Pages |
â¢Tri- and tetra substituted 1,4-benzodiazepin-3-ones were prepared in two straightforward steps.â¢The described synthetic route uses affordable and readily available building blocks.â¢A wide variety of functionalized substituents can be introduced on 1,4-benzodiazepin-3-ones.â¢The described approach gives also access to polysubstituted 1,5-benzodiazocin-4-ones.
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.
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