Atropisomeric Racemization Kinetics of MRTX1719 Using Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy

[Image: see text] With renewed interest in atropisomerism of drug molecules, efficient methods to experimentally determine torsion rotational energy barriers are needed. Here, we describe use of the chiral phosphoric acid solvating agent (+)-TiPSY to resolve the signals of atropisomers in (19)F NMR...

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Detalles Bibliográficos
Autores principales: Kulyk, Svitlana, De Paul, Susan M., Marx, Matthew A., Peakman, Torren M., Smith, Christopher R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476184/
https://www.ncbi.nlm.nih.gov/pubmed/36120049
http://dx.doi.org/10.1021/acsomega.2c03316
Descripción
Sumario:[Image: see text] With renewed interest in atropisomerism of drug molecules, efficient methods to experimentally determine torsion rotational energy barriers are needed. Here, we describe use of the chiral phosphoric acid solvating agent (+)-TiPSY to resolve the signals of atropisomers in (19)F NMR and to use the data to study the kinetics of racemization and determine the rotational energy barrier of clinical compound MRTX1719. This method is complimentary to traditional chiral high-performance liquid chromatography (HPLC) and enhances the toolkit for chiral analysis techniques.

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