Synfacts 2009(6): 0680-0680  
DOI: 10.1055/s-0029-1216771
Organo- and Biocatalysis
© Georg Thieme Verlag Stuttgart ˙ New York

Enantioselective Aza-Michael Reactions of Pyrazoles: Synthesis of INCB0184124

Contributor(s): Benjamin List, Steffen Müller
Q. Lin*, D. Meloni, Y. Pan, M. Xia, J. Rodgers, S. Shepard, M. Li, L. Galya, B. Metcalf, T.-Y. Yue, P. Liu, J. Zhou
Incyte Corporation, Wilmington, USA
Further Information

Publication History

Publication Date:
25 May 2009 (online)


The synthesis of janus kinase inhibitor INCB018424 was accomplished using an ­organocatalytic aza-Michael reaction as key step. The Hayashi-Jørgensen type catalysts 1 and 2 were found to promote the conjugate addition of different pyrazoles to (E)-3-cyclopentylacrylaldehyde in good yields and enantioselectivities. The use of acidic additives had a beneficial effect on the reaction rate, but the enantioselectivity decreased when too strong acids were used. Under optimized conditions three different pyrazoles were employed for the Michael reaction and the obtained products were further converted into the target molecule.