Facile synthesis of high specific activity 4-[1-14 C]butyl-1,2-diphenylpyrazolidine-3,5-dione (phenylbutazone) using nucleophilic substitution
| Autor: | Sara J Lupton, Anuradha Singh, Heldur Hakk |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
chemistry.chemical_classification
Base (chemistry) 010405 organic chemistry Organic Chemistry 01 natural sciences Biochemistry Medicinal chemistry 030218 nuclear medicine & medical imaging 0104 chemical sciences Analytical Chemistry Diethyl malonate Solvent 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry Bromide Yield (chemistry) Drug Discovery Nucleophilic substitution Radiology Nuclear Medicine and imaging Butyl bromide Spectroscopy Stoichiometry |
| Zdroj: | Journal of Labelled Compounds and Radiopharmaceuticals. 61:386-390 |
| ISSN: | 0362-4803 |
| Popis: | Metabolism, environmental fate, and low concentration food residue studies would be facilitated by the use of radiolabeled test articles that can be readily quantified within complex matrices. However, radiochemical approaches for such studies require high specific activities to allow analytical detection of correspondingly low masses of test article. The synthesis of high specific activity (>50 μCi/μmol) [14 C]-radiolabeled phenylbutazone presents a challenge using existing methodology, mainly due to the low solvent volumes required and vigorous refluxing needed to close the pyrazolidinedione ring. Herein, we report on the significant modification of an existing method that allows the synthesis of low masses of high specific activity (>50 μCi/μmol) [14 C]-phenylbutazone under mild conditions with simple purification and high yield. The closure of the pyrazolidinedione ring of 1,2-diphenyl-3,5-pyrazolidinedione was accomplished as a first step with unlabeled 1,2-diphenylhydrazine and diethyl malonate in 32% yield under gram-scale conditions, which avoided the challenges of low solvent use and vigorous refluxing. Low mass of high specific activity n-[1-14 C]-butyl bromide was then added via a nucleophilic substitution reaction as a final step. Yields ranged from 65% to 92% during multiple synthetic attempts with unlabeled butyl bromide and were greatly influenced by reaction stoichiometry and the selection of base. |
| Databáze: | OpenAIRE |
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