Synthesis 2020; 52(22): 3420-3426
DOI: 10.1055/s-0040-1707279
special topic
Synthesis in Industry

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

a  Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States
,
Daohong Liao
b  Pharmaron, No. 800 Bin-Hai 4th Road, Hangzhou Bay New Zone Ningbo, Zhejiang, China
,
Aleksandr Kolesnikov
a  Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States
,
Wendy Lee
a  Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States
,
Matthew L. Landry
a  Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States
› Author Affiliations
This work was supported by Genentech (a member of the Roche group).


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.

Supporting Information



Publication History

Received: 28 July 2020

Accepted: 12 August 2020

Publication Date:
15 September 2020 (online)

© 2020. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
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