Denise Rageot, F. Beaufils, Chiara Borsari
Sep 25, 2019
Citations
0
Influential Citations
6
Citations
Journal
Organic Process Research & Development
Abstract
A new, scalable, rapid, high yielding, and practical synthesis of 4-(difluoromethyl)pyridin-2-amine provides a key intermediate for the preparation of numerous protein kinase inhibitors and clinical candidates targeting phosphoinositide 3-kinase (PI3K) and the mechanistic target of rapamycin (mTOR) kinase. Starting from 2,2-difluoroacetic anhydride, an efficient five-step and two-pot procedure to prepare 4-(difluoromethyl)pyridin-2-amine (1) has been developed. Noteworthy aspects of this strategy include the avoidance of an amination process using a sealed vessel. Each step of the synthetic route has been optimized, and key intermediates have been isolated and characterized prior to the final two-pot procedure, which has been successfully applied for large-scale production.