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

J Labelled Comp Radiopharm. 2015 Aug;58(10):414-8. doi: 10.1002/jlcr.3320. Epub 2015 Jul 31.

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.

Keywords: CCR1; Crabtree's catalyst; T/H exchange; TOF-MS/MS; alkyl T/H exchange; organoiridium catalyst; tritium-NMR (3H-NMR).

MeSH terms

  • Radiopharmaceuticals / chemical synthesis*
  • Receptors, CCR1 / antagonists & inhibitors*
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Tritium / chemistry*
  • Valine / analogs & derivatives*
  • Valine / chemical synthesis
  • Valine / chemistry

Substances

  • N-(1-(4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-sulfamoylbenzamide
  • Radiopharmaceuticals
  • Receptors, CCR1
  • Sulfonamides
  • Tritium
  • Valine