Scalable, Economical, and Practical Synthesis of 4-(Difluoromethyl)pyridin-2-amine, a Key Intermediate for Lipid Kinase Inhibitors
Articolo
Data di Pubblicazione:
2019
Citazione:
Scalable, Economical, and Practical Synthesis of 4-(Difluoromethyl)pyridin-2-amine, a Key Intermediate for Lipid Kinase Inhibitors / D. Rageot, F. Beaufils, C. Borsari, A. Dall'Asen, M. Neuburger, P. Hebeisen, M.P. Wymann. - In: ORGANIC PROCESS RESEARCH & DEVELOPMENT. - ISSN 1083-6160. - 23:11(2019 Nov 15), pp. 2416-2424. [10.1021/acs.oprd.9b00312]
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
4-(difluoromethyl)pyridin-2-amine; chromatography-free process; difluoroacetic acid anhydride; pyridine ring closure; telescope process; upscaling;
Elenco autori:
D. Rageot, F. Beaufils, C. Borsari, A. Dall'Asen, M. Neuburger, P. Hebeisen, M.P. Wymann
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