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 S N Ar reactions
| Autor: | Nicolas Gerber, Eric Biron, Simon Vézina-Dawod, Xinxia Liang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
010405 organic chemistry
Peptidomimetic Organic Chemistry 010402 general chemistry Ring (chemistry) 01 natural sciences Biochemistry 0104 chemical sciences chemistry.chemical_compound chemistry Nucleophilic aromatic substitution Intramolecular force Drug Discovery Nucleophilic substitution Side chain Ugi reaction Organic chemistry Derivative (chemistry) |
| Zdroj: | Tetrahedron. 73:6347-6355 |
| ISSN: | 0040-4020 |
| DOI: | 10.1016/j.tet.2017.09.028 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect