Mild and Efficient Palladium-Mediated C-N Cross-Coupling Reaction between DNA-Conjugated Aryl Bromides and Aromatic
Eduardo de Pedro Beato1, Julián Priego1, Adrián Gironda-Martínez1
1Centro de Investigación Lilly, S. A. , 28108 Alcobendas, Madrid , Spain.
Abstract:
DNA-encoded library technology (ELT) has emerged in the pharmaceutical industry as a powerful tool for hit and lead generation. Over the last 10 years, a number of DNA-compatible chemical reactions have been published and used to synthesize libraries. Among the most commonly used reactions in medicinal chemistry is the C-N bond formation, and its application to DNA-encoded library technology affords an alternative approach to identify high-affinity binders for biologically relevant protein targets. Herein we report a newly developed Pd-promoted C-N cross coupling reaction between DNA-conjugated aryl bromides and a wide scope of arylamines in good to excellent yields. The mild reaction conditions should facilitate the synthesis of novel DNA-encoded combinatorial libraries.
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