2. Academic Validation
  3. Scalable synthesis of the VEGF-R2 kinase inhibitor JNJ-17029259 using ultrasound-mediated addition of MeLi-CeCl3 to a nitrile

Scalable synthesis of the VEGF-R2 kinase inhibitor JNJ-17029259 using ultrasound-mediated addition of MeLi-CeCl3 to a nitrile

  • J Org Chem. 2008 Feb 1;73(3):1121-3. doi: 10.1021/jo7021372.
Michael Reuman 1,  Sandra Beish,  Jeremy Davis,  Mark J Batchelor,  Martin C Hutchings,  David F C Moffat,  Peter J Connolly,  Ronald K Russell
Affiliations

Affiliation

  • 1 Johnson and Johnson Pharmaceutical Research & Development, L.L.C., 1000 Route 202, Raritan, New Jersey 08869, USA. [email protected]
PMID: 18171079 DOI: 10.1021/jo7021372
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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