Synthesis of [methoxy-3H]- and [methoxy-11C]- labelled raclopride. Specific dopamine-D2 receptor ligands

Radioactive labelled raclopride and its (R)-isomer were prepared by O-alkylation of the corresponding phenols with labelled methyl iodide. The syntheses of the two phenolic precursors from (R)- and (S)-2-aminomethyl-1-ethylpyrrolidine are described. Resolution of the racemic amine into the enantiomers was accomplished by fractional crystallization of the ditartrates. Coupling of the amines with 3,5-dichloro-2,6-dimethoxybenzoyl chloride, followed by dealkylation, led to the diphenolic precursors. Mono-alkylation of the corresponding precursor with [3H]methyl iodide furnished the potent dopamine-D2 ligand [3H]raclopride and its (R)-isomer. [11C]Methyl iodide was prepared from [11C]carbon dioxide. Subsequent reaction with phenolic (S)-precursor furnished [11C]raclopride which has been used in positron emission tomography (PET) studies of the human brain.

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