Synthesis of an Azabicyclo[3.1.0]hexanone-Containing Inhibitor of NF-κΒ Inducing Kinase via Catalytic C–H Activation

Abstract

The synthesis of an azabicyclo[3.1.0]hexanone-containing inhibitor of the nuclear factor-κB inducing kinase (NIK) is reported. The initial route to this compound was streamlined from 13 to 7 linear steps through the use of a catalytic, enantioselective C–H activation step. A procedure for lactam oxidation was identified that avoided use of peroxides on scale. These synthetic improvements allowed for the synthesis of multigram quantities of the desired NIK inhibitor for in vivo profiling.

Key words

C–H activation - NIK inhibitor - enantioselective - azabicyclo-[3.1.0]hexanone - nuclear factor-κB - medicinal chemistry

Publikationsverlauf

Eingereicht: 28. Juli 2020

Angenommen: 12. August 2020

Artikel online veröffentlicht:
15. September 2020

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