Reductive sp<sup>3</sup>–sp<sup>2</sup> Coupling Reactions Enable Late-Stage Modification of Pharmaceuticals
Katrina M. Mennie, Brandon Vara, Samuel M. Levi
Abstract
Late-stage derivatization of pharmaceutically relevant scaffolds relies on the availability of highly functional-group tolerant reactions. Reactions that increase the sp3 character of molecules enable the pursuit of more selective and well-tolerated pharmaceuticals. Herein, we report the use of sp3–sp2 cross-electrophile reductive couplings to modify a generic ATP-competitive kinase inhibitor with a broad range of primary and secondary alkyl halide coupling partners.
Topics & Concepts
ChemistryElectrophileDerivatizationHalideAlkylCombinatorial chemistryCoupling reactionCoupling (piping)MoleculeFunctional groupMedicinal chemistryOrganic chemistryCatalysisHigh-performance liquid chromatographyMechanical engineeringPolymerEngineeringCatalytic C–H Functionalization MethodsCatalytic Cross-Coupling ReactionsCyclopropane Reaction Mechanisms