Asymmetric synthesis of a precursor for the automated radiosynthesis of S-(3'-t-butylamino-2'-hydroxypropoxy)-benzimidazol-2-[11C]one (S-[11C]CGP 12177) as a preferred radioligand for beta-adrenergic receptors.

S-[1-(2,3-Diaminophenoxy)]-3'-(N-t-butylamino)propan-2'-ol has been synthesized in three steps from 2,3-dinitro-phenol and the chiral auxiliary, S-glycidyl-3-nitrobenzenesulphonate, to provide a precursor for labelling S-(3'-t-butylamino-2'-hydroxypropoxy)-benzimidazol-2-one (S-CGP 12177) with the short-lived positron-emitting radionuclide, carbon-11 (t 1/2 = 20.4 min; beta+ = 99.8%). Reaction of the diamine with [11C]phosgene, itself derived from no-carrier-added cyclotron-produced [11C]methane, provides radiochemically and chemically pure S-[carbonyl-11C]CGP 12177 in greater than 95% enantiomeric excess after HPLC. Automated apparatus is described for safely producing up to 5.9 GBq (160 mCi) of S-[11C]CGP 12177 with high sp. act. (20-40 GBq/mu mol or 0.54-1.08 Ci/mu mol) in a form suitable for human intravenous injection at only 30 min from the end of radionuclide production. S-[11C]CGP 12177 is preferred to the formerly described racemate as a radioligand for the study of beta-adrenergic receptors in vivo by positron emission tomography.