[2'-F-18]-2-OXOQUAZEPAM - SYNTHESIS OF A 5-(2-[F-18]FLUOROPHENYL)-1,4-BENZODIAZEPINE-2-ONE

The use of a 2-amino-2'-[F-18]fluorobenzhydrol as a radiolabelling int ermediate in the synthesis of a 1,4-benzodiazepine-2-one is demonstrat ed. luoro-2-(N-(2,2,2-trifluoroethyl)amino)benzhydrol, 2, was synthesi zed by the coupling of the anilinodichloroborane reagent with 2-[F-18] fluorobenzaldehyde, 1 and was subsequently oxidized to the benzophenon e, 2, using Jones reagent in 70-80% conversions after 10 min at 0-5 de grees C. After solid phase extraction, 3 reacted with bromoacetyl brom ide to generate the bromoamide, 4, in 90-95% conversions after 10 min at 140 degrees C. Ring closure of 4 to the 1,4-benzodiazepine-2-one, 5 , was accomplished using hexamethylenetetramine in aqueous dimethylsul foxide. Conversions of 80-90% were obtained after 10 min at 100 degree s C. Following preliminary cleaning by solid phase extraction, 5 was i solated by radio-HPLC. The total time of synthesis was 180-190 min and the isolated yield was on the order of 10-12% (decay-corrected) or 3- 4% (not decay-corrected) and based on [F-18]F-, The radiochemical puri ty of the isolated 1,4-benzodiazepine-2-one was >99% and the specific activity was similar to 2000 Ci/mmol at the end-of-synthesis,