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Synthesis of a high specific activity methyl sulfone tritium isotopologue of fevipiprant (NVP‐QAW039) |
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| Authors: | Van T. Luu Christian Meisterhans Matthias Frommherz Carsten Bauer |
| Affiliation: | 1. Novartis Pharma AG, Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, Basel, Switzerland;2. RC Tritec AG, Speicherstrasse, Teufen, Switzerland |
| Abstract: | The synthesis of a triple tritiated isotopologue of the CRTh2 antagonist NVP‐QAW039 (fevipiprant) with a specific activity >3 TBq/mmol is described. Key to the high specific activity is the methylation of a bench‐stable dimeric disulfide precursor that is in situ reduced to the corresponding thiol monomer and methylated with [3H3]MeONos having per se a high specific activity. The high specific activity of the tritiated active pharmaceutical ingredient obtained by a build‐up approach is discussed in the light of the specific activity usually to be expected if hydrogen tritium exchange methods were applied. |
| Keywords: | tritium CRTh2 receptor antagonists NVP‐QAV680 NVP‐QAW039 fevipiprant 3‐(2‐methyl‐7‐aza‐indolyl) acetic acid chemical cross‐linking [3H3]methyl nosylate palladium catalysis hydrogen isotope exchange |