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 |
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| Authors: | Yang Hong John Hynes Yuan Tian Balu Balasubramanian Samuel Bonacorsi Jr. |
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| Affiliation: | 1. Bristol‐Myers Squibb Research and Development, Discovery Chemistry Platforms, Princeton, NJ, USA;2. Bristol‐Myers Squibb Research and Development, Discovery Chemistry Immunology, Princeton, NJ, USA |
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| 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 3H‐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. |
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| Keywords: | CCR1 T/H exchange organoiridium catalyst Crabtree's catalyst tritium‐NMR (3H‐NMR) TOF‐MS/MS alkyl T/H exchange |
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