A synthesis of abemaciclib utilizing a Leuckart–Wallach reaction. Issue 7 (11th February 2015)

• Record Type: Journal Article
• Authors: Frederick, Michael O.; Kjell, Douglas P.
• Is Part Of: Tetrahedron letters. Volume 56:Issue 7(2015)
• Page Start: 949
• Page End: 951
• Publication Date: 2015-02-11
• Subjects: Abemaciclib -- Leuckart–Wallach reaction -- Reductive amination -- Hartwig–Buchwald coupling -- Suzuki coupling; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2014.12.082
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Abstract: A concise total synthesis of CDK 4/6 inhibitor abemaciclib is described. The synthesis uses a Suzuki coupling, followed by a Hartwig–Buchwald amination to join three of the four subunits. The final step is a reductive amination utilizing Leuckart–Wallach conditions. Key to the Leuckart–Wallach reaction was the addition of trimethyl orthoformate to remove water formed during the reaction, allowing the reaction to go to completion.