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