Synthesis of new carbon-11-labeled carboxamide derivatives as potential PET dopamine D3 receptor radioligands

Carbon-11-labeled carboxamide derivatives, (E)-4-fluoro-N-(4-(4-(2-[11C]methoxyphenyl)piperazin-1-yl)butyl)cinnamoylamide, ([11C]3a), (E)-4-chloro-N-(4-(4-(2-[11C]methoxyphenyl)piperazin-1-yl)butyl)cinnamoylamide ([11C]3b), (E)-4-bromo-N-(4-(4-(2-[11C]methoxyphenyl)piperazin-1-yl)butyl)cinnamoylamide, ([11C]3c), (E)-4-methoxy-N-(4-(4-(2-[11C]methoxyphenyl)piperazin-1-yl)butyl)cinnamoylamide ([11C]3d), N-(4-(4-(2-[11C]methoxyphenyl)piperazin-1-yl)butyl)naphthyl-2-carboxamide ([11C]BP897, [11C]3e), and N-(4-(4-(2-[11C]methoxyphenyl)piperazin-1-yl)butyl)biphenyl-4-carboxamide ([11C]3f), have been synthesized as new potential PET radioligands for imaging of dopamine D3 receptors. The target tracers were prepared by O-[11C]methylation of their corresponding precursors using [11C]CH3OTf and isolated by a simplified solid-phase extraction (SPE) purification procedure in 50–65% radiochemical yields decay corrected to end of bombardment (EOB), 20 min overall synthesis time, and 111–148 GBq/μmol specific activity at end of synthesis (EOS).