Synthesis of a tritium-labeled, fipronil-based, highly potent, photoaffinity probe for the GABA receptor.
Synthesis of a tritium-labeled, fipronil-based, highly potent, photoaffinity probe for the GABA receptor.
复制标题
DOI：
10.1021/jo034520z
复制
发表时间：
2003-09
期刊：
影响因子：
--
通讯作者：
R. Sammelson;J. Casida
中科院分区：
文献类型：
--
作者：
R. Sammelson;J. Casida
3-[4-[1-（2,6-二氯-4-三氟甲基苯基）吡唑啉]]-3-（三氟甲基）重氮嘧啶是一种基于氟虫腈（即氟虫腈）的高亲和力GABA受体探针。为了合成氚标记的三氟甲基二氮基氟丙烯（[(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]]-3-（三氟甲基）重氮嘧啶，由吡唑和3,5-二氯-4-氟苯并三氟，共10步制备。其中一个关键转化是4-（2,2,2-三氟-1-羟乙基）吡唑中间体的锂化和随后的碘化。最后一步是在乙酸乙酯中用氚、Pd/C和三乙胺还原二碘虫腈，得到比活性为15 Ci/mmol和放射性纯度为99%的[(3)H]TDF。
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.