Synthesis of a Tritium-Labeled, Fipronil-Based, Highly Potent, Photoaffinity Probe for the GABA Receptor

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 ([3H]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 [3H]TDF with a specific activity of 15 Ci/mmol and 99% radiopurity.