Scalable functionalization of azaindole derivatives for medicinal chemistry purposes

Abstract A reliable protocol for the multigram synthesis of a series of functionalized azaindoles was developed. The challenges associated with the synthesis of certain fluorine-substituted azaindole starting materials were investigated. The starting compounds were synthesized via the Sonogashira reaction under optimized conditions. A series of functionalization protocols was subsequently applied, demonstrating access to a wide range of corresponding aldehydes, acids, halogenated derivatives, sulfonyl chlorides, as well as an azatryptamine derivative. The selective hydrogenation developed in this work enabled the synthesis of a series of novel azatryptamine derivatives and 2,3-dihydroazaindoles. The developed azaindoles represents a useful class of building blocks for medicinal chemistry, offering diverse functional groups with significant potential for application in drug design.