Regioselective Synthesis of C3-Hydroxyarylated Pyrazoles

Abstract
Pyrazoles are ubiquitous structures in medicinal chemistry. We report the first regioselective route to C3-hydroxyarylated pyrazoles obtained through reaction of pyrazole N-oxides with arynes using mild conditions. Importantly, this method does not require the C4 and C5 positions of the pyrazole to be functionalized to observe regioselectivity. Using this method, we completed the synthesis of a recently reported JAK 1/2 inhibitor. Our synthesis produces the desired product in 4 steps from commercially available starting materials.
Description
Keywords
Chromatography, Ethyl groups, gels, organic compounds, silica
Citation
O’Sullivan, L., Patel, K. V., Rowley, B. C., Brownsey, D. K., Gorobets, E., Gelfand, B. S., Van Humbeck, J. F., & Derksen, D. J. (2022). Regioselective Synthesis of C3-Hydroxyarylated Pyrazoles. The Journal of Organic Chemistry, 87(1), 846–854. https://doi.org/10.1021/acs.joc.1c02518