Expedited Aminoglutarimide C-N Cross-Coupling Enabled by High-Throughput Experimentation

A simple protocol for the direct Buchwald-Hartwig cross-coupling of (hetero)aryl halides with unprotected aminoglutarimide to afford diverse Cereblon Binding Motifs is disclosed. This C-N cross-coupling method development was enabled by high throughput combinatory screening of key reaction parameters namely solvents, temperatures and ligands. Scope studies revealed generality across various heteroaryl and aryl halides, with the reaction proceeding under mild conditions. In comparison, this method demonstrated strategic superiority over previously reported approaches, as evidenced by a significant step count reduction from known syntheses in the patent literature.