Scalable Synthesis of the VEGF-R2 Kinase Inhibitor JNJ-17029259 Using Ultrasound-Mediated Addition of MeLi-CeCl3 to a Nitrile
M Reuman, S Beish, J Davis, MJ Batchelor…
文献索引：Reuman, Michael; Beish, Sandra; Davis, Jeremy; Batchelor, Mark J.; Hutchings, Martin C.; Moffat, David F. C.; Connolly, Peter J.; Russell, Ronald K. Journal of Organic Chemistry, 2008 , vol. 73, # 3 p. 1121 - 1123
The preparation of the selective VEGF-R2 kinase inhibitor 10 (JNJ-17029259) is described in which the key precursor, 4-(5-isoxazolyl) benzonitrile, undergoes clean transformation to the corresponding cumylamine derivative with CeCl3-MeLi in THF. This high-yielding cerium mediated transformation is robust, reproducible, and readily scalable based on a requirement for the anhydrous CeCl3 to be milled and subjected to ultrasound treatment ...
