General methods for the synthesis and late-stage diversification of 2, 4-substituted 7-azaindoles. Issue 42 (19th October 2016)

• Record Type: Journal Article
• Authors: Varnes, Jeffrey G.; McGuire, Thomas; Meadows, Rebecca E.; Barlaam, Bernard; Clark, Jemma; Cook, Calum R.; Davison, Gemma; Dishington, Allan; De Savi, Chris; Donald, Craig; Grebe, Tyler; Hande, Sudhir; Hawkins, Janet; Hird, Alexander W.; Holmes, Jane; Lister, Andrew; Lucas, Simon; Moore, Jane; Moore, Esther; Patel, Anil; Pike, Kurt G.; Roberts, Bryan; Stark, Andrew; Stead, Darren; Thakur, Kumar; Turner, Paul; Vasbinder, Melissa; Yang, Bin
• Is Part Of: Tetrahedron letters. Volume 57:Issue 42(2016)
• Page Start: 4718
• Page End: 4722
• Publication Date: 2016-10-19
• Subjects: 7-Azaindole -- Miyaura borylation -- Suzuki–Miyaura reaction -- 1H-Pyrrolo[2, 3-b]pyridine -- 2-(Piperidin-4-yl)-7-azaindole; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2016.09.029
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Methods for preparing 2, 4-substituted 7-azaindoles are compared. An iterative catalyst screen was used to optimize borylation conditions. A scalable synthesis of 4-bromo-2-(piperidin-4-yl)-7-azaindole is described. Abstract: As part of a medicinal chemistry program, we adapted known synthetic methods for the late-stage diversification of 2, 4-substituted 7-azaindoles. The strengths and weaknesses of these strategies are discussed. In the course of this work, three optimized conditions were identified from an iterative catalyst screen for the conversion of Boc-protected 4-chloro-2-(piperidin-4-yl)-7-azaindole to the corresponding pinacol borate ester. Additionally, a scalable route to previously unreported Boc-protected 4-bromo-2-(piperidin-4-yl)-7-azaindole and efficient conversion to the corresponding pinacol borate ester in 72% isolated yield are also disclosed.