Synthesis of Aminopyrazoles from Isoxazoles: Comparison of Preparative Methods by in situ NMR Analysis
Neil J. Kallman, Kevin P. Cole, Thomas M. Koenig, Jonas Y. Buser, Adam D. McFarland, LuAnne M. McNulty, David Mitchell*
*Lilly Research Laboratories, Eli Lilly and Company,
Indianapolis, IN 46285, USA, Email: dmit
lilly.com
N. J. Kallman, K. P. Cole, T. M. Koenig, J. Y. Buser, A. D. McFarland, L. M. McNulty, D. Mitchell, Synthesis, 2016, 48, 3537-3543.
DOI: 10.1055/s-0035-1561861
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Abstract
In a single-step method for the synthesis of aminopyrazoles from isoxazoles, hydrazine serves to open the isoxazole to the unisolated ketonitrile intermediate and form the aminopyrazole. The two-step process involves ring opening of the isoxazole by deprotonation with hydroxide to generate the ketonitrile followed by the addition of acetic acid and hydrazine to form the aminopyrazole.
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Key Words
aminopyrazoles, pyrazoles, isoxazoles, in situ NMR analysis, ketonitriles, heterocycles, regioselectivity
ID: J66-Y2016
