title: Synthesis and characterization of tritium labeled N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-sulfamoylbenzamide.
abstract: N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-sulfamoylbenzamide is a potent C-C chemokine receptor 1 (CCR1) antagonist. The compound, possessing benzamide functionality, successfully underwent tritium/hydrogen (T/H) exchange with an organoiridium catalyst (Crabtree's catalyst). The labeling pattern in the product was studied with liquid chromatography-mass spectrometry, time-of-flight mass spectrometry, and (3) H-NMR. Overall, multiple labeled species were identified. In addition to the anticipated incorporation of tritium in the benzamide moiety, tritium labeling was observed in the valine portion of the molecule including substitution at its chiral carbon. Using authentic standards, liquid chromatography analysis of the labeled compound showed complete retention of stereochemical configuration.
authors.affiliation: Bristol-Myers Squibb Research and Development, Discovery Chemistry Platforms, Rt 206 and Province Line Road, Princeton, NJ, 08540, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Bristol-Myers Squibb Research and Development, Discovery Chemistry Immunology, Rt 206 and Province Line Road, Princeton, NJ, 08540, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hynes
authors.affiliation: Bristol-Myers Squibb Research and Development, Discovery Chemistry Platforms, Rt 206 and Province Line Road, Princeton, NJ, 08540, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Bristol-Myers Squibb Research and Development, Discovery Chemistry Platforms, Rt 206 and Province Line Road, Princeton, NJ, 08540, USA.
authors.forename: Balu
authors.initials: B
authors.lastname: Balasubramanian
authors.affiliation: Bristol-Myers Squibb Research and Development, Discovery Chemistry Platforms, Rt 206 and Province Line Road, Princeton, NJ, 08540, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Bonacorsi
mesh_terms: D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry; D014316:Tritium / Q000737:chemistry*; D014633:Valine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: C000608516:N-(1-(4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-sulfamoylbenzamide; D019275:Radiopharmaceuticals; D054389:Receptors, CCR1; D013449:Sulfonamides; D014316:Tritium; D014633:Valine
keywords: CCR1; Crabtree's catalyst; T/H exchange; TOF-MS/MS; alkyl T/H exchange; organoiridium catalyst; tritium-NMR (3H-NMR)