DNA-Compatible α-Aminoamide Synthesis for a DNA-Encoded Library.

We report the first direct solution-phase on-DNA Ugi three-component reaction for the selective synthesis of α-aminoamides under mild, DNA-compatible conditions. The optimized reaction provides selective access to the desired products by minimizing competing reaction pathways. The method exhibits broad substrate scope for DNA-conjugated anilines and is applicable to representative DNA-conjugated aldehydes and isocyanides. This work expands the repertoire of DNA-compatible multicomponent reactions and provides access to privileged α-aminoamide scaffolds for DNA-encoded libraries.