Sammelson Robert E, Casida John E
Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720-3112, USA.
J Org Chem. 2003 Oct 17;68(21):8075-9. doi: 10.1021/jo034520z.
3-[4-[1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazolo]]-3-(trifluoromethyl)diazirine is a fipronil-based (i.e. fiprole), high-affinity probe for the GABA receptor. For synthesis of the tritium-labeled version of this trifluoromethyldiazirinylfiprole ([(3)H]TDF) the required intermediate, 3-[4-[1-(2,6-dichloro-3-iodo-4-trifluoromethylphenyl)-5-iodopyrazolo]]-3-(trifluoromethyl)diazirine, was prepared in 10 steps from pyrazole and 3,5-dichloro-4-fluorobenzotrifluoride. One of the key transformations was lithiation and subsequent iodination of the 4-(2,2,2-trifluoro-1-hydroxyethyl)pyrazole intermediate. The last step involved reduction of the diiodofiprole with tritium, Pd/C, and triethylamine in ethyl acetate and afforded [(3)H]TDF with a specific activity of 15 Ci/mmol and 99% radiopurity.
3-[4-[1-(2,6-二氯-4-三氟甲基苯基)吡唑并]]-3-(三氟甲基)二氮杂环丙烷是一种基于氟虫腈（即氟吡咯）的、对γ-氨基丁酸受体具有高亲和力的探针。为了合成这种三氟甲基二氮杂环丙烷氟虫腈的氚标记版本（[(3)H]TDF），所需的中间体3-[4-[1-(2,6-二氯-3-碘-4-三氟甲基苯基)-5-碘吡唑并]]-3-(三氟甲基)二氮杂环丙烷由吡唑和3,5-二氯-4-氟苯并三氟化物经10步反应制备而成。关键转化步骤之一是对4-(2,2,2-三氟-1-羟乙基)吡唑中间体进行锂化反应及后续碘化反应。最后一步是在乙酸乙酯中用氚、钯/碳和三乙胺还原二碘氟虫腈，得到比活度为15 Ci/mmol且放射化学纯度为99%的[(3)H]TDF。
