P. Johnstrom et al., [2'-F-18]-2-OXOQUAZEPAM - SYNTHESIS OF A 5-(2-[F-18]FLUOROPHENYL)-1,4-BENZODIAZEPINE-2-ONE, Journal of labelled compounds & radiopharmaceuticals, 34(2), 1994, pp. 147-156
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,