Reagent-Based Diversity-Oriented Synthesis of Triazolo[1,5-a][1,4]diazepine Derivatives from Polymer-Supported Homoazidoalanine

Abstract

Herein, we report the synthesis of skeletally different triazolo­[1,5-a]­[1,4]­diazepines starting from immobilized homoazidoalanine. After sulfonylation with 2/4-nitrobenzenesulfonyl chlorides and Mitsunobu alkylation with various alkynols, the corresponding N-substituted nitrobenzenesulfonamides were obtained. Their catalyst-free Huisgen cycloaddition provided immobilized and functionalized triazolo­[1,5-a]­[1,4]­diazepines as the key intermediates for further modification. Using the concept of diversity-oriented, reagent-based synthesis, the key intermediates were subsequently converted to heterocycles bearing [5 + 7 + 5], [5 + 7 + 6], and [5 + 7 + 7] scaffolds. Furthermore, the synthesis of spirocyclic triazolodiazepines was developed.

Diketomorpholines: Synthetic Accessibility and Utilization

“…An analogous protocol could be used for the solid-phase-supported generation of tricyclic DKMs 29 ( Scheme 8 ). 20 …”

Efficient synthesis of pentasubstituted pyrroles via intramolecular C-arylation

“…43,44 Recently, we focused on the application of amino acids with functionalized side chains, e.g. serine or azidoalanine, which yielded various morpholines 45 or triazolodiazepines, 46,47 respectively. In the current project, we intended to use Fmoc-Asp(OMe)-OH to ultimately synthesize analogical intermediates with the side-chain carboxylic group amenable for further modification.…”