Application of LC-NMR and HR-NMR to the characterization of biphenyl impurities in the synthetic route development for vestipitant, a novel NK1 antagonist

J Pharm Biomed Anal. 2010 Nov 2;53(3):389-95. doi: 10.1016/j.jpba.2010.04.027. Epub 2010 Apr 29.

Abstract

Vestipitant (1) is a novel NK1 antagonist currently under investigation for the treatment of CNS disorders and emesis. The first synthetic step comprised a Grignard synthesis. An impurity was identified and initially expected to be a symmetric biphenyl. This paper reports the work to synthesise the supposed structure and the spectroscopic analyses (LC-NMR and HR-NMR) to correctly identify the real structure and understand the chemical pathway of the impurity.

MeSH terms

  • Biphenyl Compounds / chemistry*
  • Chromatography, High Pressure Liquid
  • Drug Contamination*
  • Fluorobenzenes
  • Magnetic Resonance Spectroscopy / methods*
  • Neurokinin-1 Receptor Antagonists*
  • Piperidines / chemical synthesis
  • Piperidines / chemistry*

Substances

  • Biphenyl Compounds
  • Fluorobenzenes
  • Neurokinin-1 Receptor Antagonists
  • Piperidines
  • biphenyl
  • vestipitant