An expedient and facile route for the general synthesis of 3-aryl substituted 1,2,3-triazolo[1,5-a][1,4]benzodiazepin-6-ones and 1,2,3-triazolo[1,5-a][1,5]benzodiazocin-7-ones

Abstract

We describe herein a convenient approach for the general synthesis of novel tricyclic scaffolds incorporating a fusion of the 1,2,3-triazole ring with difficultly obtainable medium sized rings such as [1,4]benzodiazepin-5-ones and [1,5]benzodiazocin-6-ones through Sonogashira coupling of an aryl iodide with 2-amino-N-methyl-N-(prop-2-ynyl)benzamide or homologue followed by in situ diazotisation, azidation and cycloaddition reactions. The strategy also allows easy accessibility of the corresponding amide-reduced analogues. The operational simplicity and easy substrate availability make the process cost effective and practical.

Copper-Catalyzed Tandem Reactions of 2-Iodobenzamides with Sodium Azide: An Efficient Synthesis of [1,2,3]Triazolo[1,5-a][1,4]-benzodiazepin-6(5H)-ones

“…In summary, we have developed an efficient method for the synthesis of 3-substituted [1,2,3]triazolo [1,5-a][1,4]benzodiazepin-6(5H)-ones in moderate yields under mild conditions which could be converted into other interesting and useful structural units. 8 Further studies concerning the scope, mechanism, and synthetic applications of this transformation are being carried out in our laboratory.…”

“…However, careful examination of the literature indicates that most of its syntheses 7 have been developed for specific derivatives (R 1 = H) of 4. For the 3-substituted derivatives (R 1 = aryl, alkyl) of 4 is rarely pursued, Chowdhury, 8 Zecchi, 9 and coworkers have described a multistep approach involving diazotization, azidation, and cycloaddition procedures, respectively.…”

An Efficient One-Pot Strategy for the Synthesis of Triazole-Fused 1,4-Benzodiazepinones from N-Substituted 2-Azidobenzamides

“…Hemming and co-workers 14 reported the synthesis of triazolobenzodiazepines and pyrrolobenzodiazepines using an intramolecular 1,3-dipolar cycloaddition in a multistep process. Furthermore, Chowdhury 15 has described an approach for the synthesis of 1,2,3-triazolo[1, 5a] [1,4]benzodiazepin-6-ones and 1,2,3-triazolo[1, 5a] [1,5]benzodiazocin-7-ones through Sonogashira coupling of an aryl iodide with 2-amino-N-methyl-N-(prop-2ynyl)benzamide or its homologue, followed by in situ diazotization, azidation and cycloaddition reactions. The Lemrova 16 group have reported a solid-phase synthesis of 1,2,3,4-tetrahydrobenzo [e][1,4]diazepin-5-ones using polystyrene resin.…”

Copper‐Free Solid‐Phase Synthesis of Triazolo[1,5‐a][1,4]diazepin‐6‐ones

“…Recently, we developed a solid‐phase synthesis method for triazolobenzodiazepinones based on the spontaneous AAC of immobilized propargyl‐azidobenzamides [9] . The preparation of triazolobenzodiazepinones was also reported by others using different approaches [10–15] . In contrast, the synthesis of parent triazolodiazepinones has rarely been studied.…”