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 ([(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.
Sammelson
Robert E
RE
Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720-3112, USA.
Casida
John E
JE
D001389:Azirines / Q000138:chemical synthesis* / Q000737:chemistry; D018756:GABA Antagonists / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D019920:Photoaffinity Labels / Q000138:chemical synthesis* / Q000737:chemistry; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D014316:Tritium
C482088:3-(4-(1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazolo))-3-(trifluoromethyl)diazirine; D001389:Azirines; D018756:GABA Antagonists; D019920:Photoaffinity Labels; D011720:Pyrazoles; D014316:Tritium; C082360:fipronil