Scalable synthesis of the VEGF-R2 kinase inhibitor JNJ-17029259 using ultrasound-mediated addition of MeLi-CeCl3 to a nitrile |
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Authors: | Reuman Michael Beish Sandra Davis Jeremy Batchelor Mark J Hutchings Martin C Moffat David F C Connolly Peter J Russell Ronald K |
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Institution: | Johnson and Johnson Pharmaceutical Research & Development, L.L.C., 1000 Route 202, Raritan, New Jersey 08869, USA. mreuman@prdus.jnj.com |
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Abstract: | 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 CeCl(3)-MeLi in THF. This high-yielding cerium mediated transformation is robust, reproducible, and readily scalable based on a requirement for the anhydrous CeCl(3) to be milled and subjected to ultrasound treatment prior to addition of methyllithium. |
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