The purpose of this project was to synthesize WAY-100635, {N-[2-[4-(2- methoxyphenyl)-l-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide trihydrochloride), labeled with carbon-11 (T1/2 = 20.4 min), a cyclotron produced, positron-emitting radionuclide. Dr. Markku Linnoila is interested in studying this highly selective and potent 5-HT1A serotonin receptor antagonist. Changes in 5-HT1A receptors have been implicated in several neuropsychiatric diseases, including anxiety, depression, and Alzheimer's disease. WAY- 100635 is amenable to labeling with carbon-11 and two procedures on its synthesis have been reported. Methylation of (desmethyl)WAY-100635 with [11C]CH3I followed by HPLC gave [O-methyl- 11C]WAY-100635 in high radiochemical yield and radiopurity. We have been adapting these procedures to the development of [O-methyl-11C]WAY-100635 in our laboratory. Dr. Linnoila required some unlabeled WAY-100635 for tox-path studies and we provided him with 600 mg of pure material. In one synthesis of unlabeled WAY-100635, WAY-100634 {(decyclohexylcarbonyl)WAY-100635} is produced. This is converted to WAY- 100635 by reaction with cyclohexanecarbonyl chloride. We have not been able to convert WAY-100635 to pure (desmethyl)WAY-100635, which is the precursor to [11C]WAY-100635, by this method. (Desmethyl)Way- 100635 can be obtained by another method. In this other method, WAY-100634 is converted to (desmethyl)WAY-100634, which is then converted to (desmethyl)WAY-100635 with cyclohexanecarbonyl chloride. By this method we have synthesized pure (desmethyl)WAY- 100634, and are in the process of converting it to (desmethyl)WAY- 100635.
