An improved method for the synthesis of radiolabeled McN5652 via thioester precursors

An improved procedure that facilitates routine production and increases the radiochemical yield of [11C]McN5652 (trans-1,2,3,5,6,10b-hexahydro-6-[4-([11C]methylthio)-phenyl]pyrrolo- [2,1-alpha]-isoquinoline) is presented. Specifically, thiol acetate, butyrate, and benzoate derivatives of McN5652 were prepared as the precursors for the [11C]McN5652 synthesis. These thioesters offer greater stability than the previously used thiol precursor (desmethyl McN5652) and enable a single batch of material to be used for multiple radiolabelings. Hydrolysis of the thioester functionality (tetrabutylammonium hydroxide, 10 min) unmasked the free thiol which, without purification, was reacted with [11C]iodomethane in DMF at 40-45 degrees C for 1 min. The average decay-corrected radiochemical yield for [11C]McN5652 was 26% with an average specific activity of 2290 mCi/mumol (end of synthesis). This facile radiolabeling method, utilizing the butyrate thioester of McN5652, was also employed in the preparation of [3H](+)- and (-)McN5652 [trans-1,2,3,5,6S (or 6R),10bR, (or 10bS)-hexahydro-6-[4-([3H]methylthio)phenyl]pyrrolo-[2,1,alpha]- isoquinoline] from [3H]iodomethane.