[11C]olanzapine, radiosynthesis and lipophilicity of a new potential PET 5-HT2 and D2 receptor radioligand.

Olanzapine and its precursor desmethyl-Olanzapine were synthesized from malononitrile, propionaldehyde, 1-fluoro-2-nitrobenzene, and substituted piperazine in 4, 4, 5, and 5 steps with 35%, 32%, 26%, and 32% overall chemical yield, respectively. [(11)C]Olanzapine was prepared from desmethyl-Olanzapine with [(11)C]CH3OTf through N-[(11)C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 40-50% radiochemical yield based on [(11)C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/µmol specific activity at EOB. The calculated LogP (CLogP) value of [(11)C]Olanzapine is 3.39.