[2′‐18F]‐2‐oxoquazepam: Synthesis of a 5‐(2‐[18F]fluorophenyl)‐1,4‐benzodiazepine‐2‐one

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.