Synthesis and11C-radiolabelling of a tropane derivative lacking the 2β ester group: a potential PET-tracer for the dopamine transporter

The synthesis and 11 C-radiolabelling of a new tropane analogue. 3β-(4'-chlorophenyl)-2β-(3'-phenylisoxazol-5'-yl)tropane (β-CPPIT), an inhibitor of the dopamine transporter, is reported. The desmethyl compound, 3β-(4'-chlorophenyl)-2β-(3'-phenylisoxazol-5'-yl)nortropane (5) was prepared via a six-step reaction sequence starting from cocaine. [ 11 C]-β-CPPIT was labelled by N-methylation using [ 11 C]-methyl iodide obtained from the gas phase reaction of [ 11 C]-methane with iodine in 60 ± 10 % radiochemical yield (decay corrected from [ 11 C]-methyl iodide). The overall synthesis time was on average 60 minutes at EOB (end of bombardment). The final product had a specific activity of 2000 - 2700 Ci/mmol (74 - 100 TBq/mmol) at EOS (end of synthesis) and the radiochemical purity was greater than 99%. [ 11 C]-β-CPPIT showed a logP value of 2.1 indicating that a free diffusion through the blood-brain-barrier should be possible.