Synthesis of 1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)-[Methyl-11C]thymine ([11C]FMAU) via a Stille cross-coupling reaction with [11C]methyl iodide

1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-[methyl-C-11]thymine ([C-11]FMAU) [C-11]-(1) under bar was synthesised via a palladium-mediated Stille coupling reaction of 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-(trimethylstannyl)uracil (2) under bar with [C-11]methyl iodide in a one-pot procedure. The reaction conditions were optimized by screening various catalysts and solvents, and by altering concentrations and reaction temperatures. The highest yield was obtained using Pd-2(dba)(3) and P(o-tolyl)(3) in DMF at 130degreesC for 5 min. Under these conditions the title compound [C-11]-(1) under bar was obtained in 28 +/- 5% decay-corrected radiochemical yield calculated from [C-11]methyl iodide (number of experiments=7). The radiochemical purity was >99% and the specific radioactivity was 0.1GBq/mumol at 25 min after end of bombardment. In a typical experiment 700-800 MBq of [C-11]FMAU [C-11]-(1) under bar was obtained starting from 6-7 GBq of [C-11]methyl iodide. A mixed C-11/C-13 synthesis to yield [C-11]-(1) under bar/(C-13)-(1) under bar followed by C-13-NMR analysis was used to confirm the labelling position. The labelling procedure was found to be suitable for automation. Copyright (C) 2002 John Wiley Sons, Ltd.