The labelling of a novel tropane derivative [¹¹C]NS 2214 (BMS-204756) - An inhibitor of the dopamine transporter

The ¹¹C-labelling of a novel tropane derivative (+)-(E)-(1R,2R,3S)-3-(3,4-dichlorophenyl)-8-[¹¹C]methyl-8 -azabicyclo[3.2.1]octane-2-O-methyl-aldoxime (NS 2214 or BMS-204756), an inhibitor of the dopamine transporter (IC₅₀ 3 nM) is reported. (+)-(E)-(1R,2R,3S)-3-(3,4-dichlorophenyl)-8-azabicyclo[3.2.1]octane-2-O-methyl -aldoxime (NS 2262, either as the disulphate salt with added base or as the free amine) was alkylated with [¹¹C]methyl iodide. The crude product was purified by HPLC using either a reverse phase or cyanopropyl stationary phase. Best results were obtained using the free amine as the labelling precursor and the cyanopropyl stationary phase for the HPLC purification. This resulted in the synthesis of radiochemically pure [¹¹C]NS 2214 with a decay corrected radiochemical yield of 24-30%, specific activity > 50 GBq/μmol (>1.4 Ci/μmol), and a total synthesis time of less than 30 min (counted from EOB).