Synthesis and in vivo evaluation of [ O ‐methyl‐ 11 C] 2‐(4‐methoxyphenyl)‐ N ‐(4‐methylbenzyl)‐ N ‐(1‐methyl‐ piperidin‐4‐yl)acetamide as an imaging probe for 5‐HT 2A receptors

2‐(4‐Methoxyphenyl)‐ N ‐(4‐methylbenzyl)‐ N ‐(1‐methylpiperidin‐4‐yl)acetamide (AC90179, 4 ), a highly potent and selective competitive 5‐HT 2A antagonist, was labeled by [ 11 C]‐methylation of the corresponding desmethyl analogue 5 with [ 11 C]methyl triflate. The precursor molecule 5 for radiolabeling was synthesized from p ‐tolylmethylamine in three steps with 46% overall yield. [ 11 C]AC90179 was synthesized in 30 min (30 ± 5% yield, EOS) with a specific activity of 4500 ± 500 Ci/mmol and >99% chemical and radiochemical purities. Positron emission tomography studies in anesthetized baboon revealed that [ 11 C] 4 Penetrates the blood–brain barrier (BBB) with a rapid influx and efflux of the tracer in all brain regions. Due to lack of tracer retention or specific binding, [ 11 C] 4 cannot be used as PET ligand for imaging 5‐HT 2A receptors. Copyright © 2006 John Wiley & Sons, Ltd.