Application of LC-NMR and HR-NMR to the characterization of biphenyl impurities in the synthetic route development for vestipitant, a novel NK1 antagonist.
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.
Provera
Stefano
S
Analytical Chemistry, GlaxoSmithKline Medicines Research Centre, Via Fleming 4, 37135 Verona, Italy. stefano.2.provera@gsk.com
Martini
Luca
L
Guercio
Giuseppe
G
Turco
Lucilla
L
Costa
Laura
L
Marchioro
Carla
C
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*
D001713:Biphenyl Compounds; D005464:Fluorobenzenes; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; C010574:biphenyl; C534550:vestipitant