Efficient reductive amination using continuous flow devices accelerates hit-to-lead process

ORGN 635

Attila Wootsch, Éva Kapuvári, eva.kapuvari@thalesnano.com, Eszter Varga, Zsolt Ötvös, György Bene, György Dormán, László Ürge, Ferenc Darvas, and Richard Jones. ThalesNano Inc, H-1031 Záhony u. 7, Budapest, Hungary
Reductive amination provides a robust approach enabling to connect large number of pharmacologically relevant building blocks (fragments) having an aldehyde (or ketone) and amine functionality. However, the traditional batch-based approaches have several hurdles such as incomplete reaction, side products and hydrogenation requires special lab safety requirements. Using continuous flow devices offers a one-step practical solution to these difficulties. H-Cube®, is a bench-top standalone hydrogenation reactor, which uniquely combines continuous-flow microchemistry with endogenous on-demand hydrogen generation and a disposable catalyst cartridge system. It allows fast and cost-efficient hydrogenation with superior yield in the standard organic synthesis lab. The presentation will describe numerous examples where various building blocks including substituted cyclohexanones, piperidinones and aniline derivatives can be efficiently coupled creating a secondary amine library. The rapid reaction optimization process will also be discussed.