Synthesis of 3-[(1-[11C]methyl-2(S)-pyrrolidinyl) methoxy]pyridine and 3-[(1-[11C]methyl-2(R)-pyrrolidinyl) methoxy]pyridine: Radioligands for in vivo studies of neuronal nicotinic acetylcholine receptors

Abstract

3-[(1-[11C]Methyl-2(S)-pyrrolidinyl)methoxy]pyridine, [11C]A-84543, a selective radioligand for neuronal nicotinic acetylcholine receptors (nAChRs) was prepared by N-alkylation of N-desmethyl A-84543 with [11C]methyl iodide in DMF. The radioligand was purified by semi-preparative reverse-phase HPLC. The average specific radioactivity was 1755 mCi/μmol calculated at end-of-synthesis (EOS). The average time of synthesis, including formulation, was 17 min. The pharmacologically less active (R) enantiomer, 3-[(1-[11C]methyl-2(R)-pyrrolidinyl) methoxy]pyridine was synthesized in an analogous manner using the appropriate N-desmethyl precursor. The specific radioactivity was calculated to be 2368 mCi/μmol (EOS). © 1997 John Wiley & Sons, Ltd.