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

✍ Scribed by Linda Samuelsson; Bengt Långström

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: French
• Weight: 114 KB
• Volume: 46
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.668

✦ Synopsis

Abstract

1‐(2′‐deoxy‐2′‐fluoro‐β‐D‐arabinofuranosyl)‐[methyl‐^11^C]thymine ([^11^C]FMAU) [^11^C]‐1 was synthesised via a palladium‐mediated Stille coupling reaction of 1‐(2′‐deoxy‐2′‐fluoro‐β‐D‐arabinofuranosyl)‐5‐(trimethylstannyl)uracil 2 with [^11^C]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 130°C for 5 min. Under these conditions the title compound [^11^C]‐1 was obtained in 28±5% decay‐corrected radiochemical yield calculated from [^11^C]methyl iodide (number of experiments=7). The radiochemical purity was >99% and the specific radioactivity was 0.1 GBq/μmol at 25 min after end of bombardment. In a typical experiment 700–800 MBq of [^11^C]FMAU [^11^C]‐1 was obtained starting from 6–7 GBq of [^11^C]methyl iodide. A mixed ^11^C/^13^C synthesis to yield [^11^C]‐1/(^13^C)‐1 followed by ^13^C‐NMR analysis was used to confirm the labelling position. The labelling procedure was found to be suitable for automation. Copyright © 2002 John Wiley & Sons, Ltd.