title: Application of LC-NMR and HR-NMR to the characterization of biphenyl impurities in the synthetic route development for vestipitant, a novel NK1 antagonist.
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.
authors.affiliation: Analytical Chemistry, GlaxoSmithKline Medicines Research Centre, Via Fleming 4, 37135 Verona, Italy. stefano.2.provera@gsk.com
authors.forename: Stefano
authors.initials: S
authors.lastname: Provera
authors.forename: Luca
authors.initials: L
authors.lastname: Martini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Guercio
authors.forename: Lucilla
authors.initials: L
authors.lastname: Turco
authors.forename: Laura
authors.initials: L
authors.lastname: Costa
authors.forename: Carla
authors.initials: C
authors.lastname: Marchioro
mesh_terms: D001713:Biphenyl Compounds / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D005464:Fluorobenzenes; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D001713:Biphenyl Compounds; D005464:Fluorobenzenes; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; C010574:biphenyl; C534550:vestipitant