Copper-Mediated Three-Component Reaction for the Synthesis of <i>N</i>-Sulfonylamidine on DNA

DNA-encoded library (DEL) technology is a transformative tool for identifying bioactive compounds in pharmaceutical research. This study presents an optimized copper-mediated reaction to synthesize <i>N</i>-sulfonylamidine derivatives from DNA-conjugated alkynes and sulfonyl azides under mild conditions. Amines serve as nucleophiles, enabling selective functionalization under mild conditions while preserving DNA integrity. Through systematic refinement of reaction conditions and substrate evaluation, the approach demonstrated a high tolerance to diverse functional groups, significantly expanding DEL-accessible chemical space. The developed DNA-compatible method underscores the role of DELs in enhancing drug discovery by facilitating the introduction of novel pharmacophores into compound libraries.