Enantioselective synthesis of GNE-6688, a potent and selective inhibitor of interleukin-2 inducible T-cell kinase (ITK). Issue 11 (14th March 2019)

• Record Type: Journal Article
• Authors: Moore, Jared; Lau, Kevin; Xu, Xiaofeng; Zhang, Yamin; Burch, Jason D.
• Is Part Of: Tetrahedron letters. Volume 60:Issue 11(2019)
• Page Start: 785
• Page End: 788
• Publication Date: 2019-03-14
• Subjects: Kinase inhibitors -- Enantioselective catalysis -- Directed cyclopropanation -- Transfer hydrogenation -- Allylboration; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2019.02.014
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: A stereoselective synthesis of the ITK inhibitor GNE-6688 has been accomplished. An enantioselective transfer hydrogenation was used to prepare the Western fragment. An enantioselective allylboration, and a directed cyclopropanation were key steps for the Eastern fragment. Abstract: An enantioselective synthesis of the previously-disclosed ITK inhibitor GNE-6688 is described. Synthesis of the nitropyrazole fragment is highlighted by a Ru-catalyzed transfer hydrogenation using the Wills tethered ligand system. Synthesis of the pyrazole carboxylic acid fragment features an allylboration catalyzed by a chiral diol-SnCl4 complex, followed by a highly diastereoselective directed cyclopropanation.