A convergent preparation of the CHK1 inhibitor MK-8776 (SCH 900776). Issue 24 (15th June 2016)

• Record Type: Journal Article
• Authors: Labroli, Marc A.; Dwyer, Michael P.; Poker, Cory; Keertikar, Kerry M.; Rossman, Randall; Guzi, Timothy J.
• Is Part Of: Tetrahedron letters. Volume 57:Issue 24(2016)
• Page Start: 2601
• Page End: 2603
• Publication Date: 2016-06-15
• Subjects: Kinase -- CHK1 -- MK-8776 -- Serine/threonine kinase -- Oncology; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2016.04.102
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: A highly convergent preparation of the CHK1 inhibitor MK-8776 is described. Efficient cyclocondensation reaction to form the pyrazolo[1, 5- a ]pyrimidine core. Key insights made into the retention of optical purity during the cyclocondensation reaction. Abstract: This Letter describes the development of a convergent, efficient route to the CHK1 inhibitor MK-8776. This synthetic approach relies upon the cyclization of a bispyrazole adduct10 with a optically pure β-keto nitrile9 to construct the pyrazolo[1, 5- a ]pyrimidine scaffold in a single step.