Rapid in situ synthesis of [11C]methyl azide and its application in 11C click-chemistry

✍ Scribed by Ralf Schirrmacher; Younes Lakhrissi; Dean Jolly; Julian Goodstein; Philippe Lucas; Esther Schirrmacher

• Publisher: Elsevier Science
• Year: 2008
• Tongue: French
• Weight: 224 KB
• Volume: 49
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/j.tetlet.2008.06.020

✦ Synopsis

We synthesized [ 11 C]methyl azide ([ 11 C]MeA) by reacting [ 11 C]methyl iodide ([ 11 C]MeI) in situ with an azide-donor and used it in the synthesis of 11 C-labeled 1,2,3-triazoles. A one-pot click approach comprised the infusion of gaseous [ 11 C]MeI into a mixture of NaN 3 , ethynylbenzene, and CuI in water at a temperature of 100 °C yielding the 11 C-triazole in radiochemical yields (RCY) of 25%. In a two-step labeling protocol, we synthesized the [ 11 C]MeA in acetonitrile in advance to the click step. Using the more soluble Na þ =18-crown-6=N À 3 complex as source of N 3 À , a much higher trapping efficiency of [ 11 C]MeI in this solvent ensured an almost quantitative conversion of [ 11 C]MeI to [ 11 C]MeA within 5-10 min at room temperature. The [ 11 C]MeA was thereafter reacted with ethynylbenzene at 100 °C yielding 1-[ 11 C]methyl-4-phenyl-1H-1,2,3-triazole in preparative RCY of 60%. As a final proof of applicability, we used 11 C-click-chemistry for the labeling of N-terminal 4-ethynylbenzene derivatized D-Glu-D-Tyr-[Cys-Tyr-Trp-Lys-Thr-Cys]-Thr, a cyclic water-soluble Tyr 3 -octreotate derivative.