Peter Johnströma, S. Stone-Elander, T. Duelfer
Feb 1, 1994
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0
Influential Citations
5
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Journal
Journal of Labelled Compounds and Radiopharmaceuticals
Abstract
The use of a 2-amino-2′-[18F]fluorobenzhydrol as a radiolabelling intermediate in the synthesis of a 1,4-benzodiazepine-2-one is demonstrated. 5-Chloro-2′-[18F]fluoro-2-(N-(2,2,2-trifluoroethyl)amino)benzhydrol, 2, was synthesized by the coupling of the anilinodichloroborane reagent with 2-[18F]fluorobenzaldehyde, 1 and was subsequently oxidized to the benzophenone, 3, using Jones reagent in 70–80% conversions after 10 min at 0–5°C. After solid phase extraction, 3 reacted with bromoacetyl bromide to generate the bromoamide, 4, in 90–95% conversions after 10 min at 140°C. Ring closure of 4 to the 1,4-benzodiazepine-2-one, 5, was accomplished using hexamethylenetetramine in aqueous dimethylsulfoxide. Conversions of 80–90% were obtained after 10 min at 100°C. Following preliminary cleaning by solid phase extraction, 5 was isolated by radio-HPLC. The total time of synthesis was 180–190 min and the isolated yield was on the order of 107ndash;12% (decay-corrected) or 3–4% (not decay-corrected) and based on [18F]F−. The radiochemical purity of the isolated 1,4-benzodiazepine-2-one was >99% and the specific activity was ∼2000 Ci/mmol at the end-of-synthesis.