Accelerated Synthesis of Bicyclo[1.1.1]pentylamines: A High-Throughput Approach

• DOI: 10.1021/acs.orglett.2c04226
• Publication Date: 2023-02-01T23:13:40Z
• Authors: Maialen Alonso; Santiago Cañellas; Francisca Delgado; Marta Serrano; Alejandro Diéguez...; José Enrique Gómez
• Keywords: Leverage (statistics); Chemical space

Strained bicyclic substructures such as bicyclo[1.1.1]pentylamines (BCPAs) are increasingly targeted in medicinal chemistry arylamine bioisosteres. Here, we leverage high-throughput automated synthesis to rapidly develop library-amenable reaction conditions and maximize design space expand access BCPAs. This new protocol relies on a copper-mediated C–N coupling approach uses accessible bench-stable iodo-BCP building blocks. Its applicability has been exemplified by incorporating BCPs drug-like compounds, providing straightforward library of valuable aniline-like isosteres.