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

We synthesized [11C]methyl azide ([11C]MeA) by reacting [11C]methyl iodide ([11C]MeI) in situ with an azide-donor and used it in the synthesis of 11C-labeled 1,2,3-triazoles. A one-pot click approach comprised the infusion of gaseous [11C]MeI into a mixture of NaN3, ethynylbenzene, and CuI in water at a temperature of 100 °C yielding the 11C-triazole in radiochemical yields (RCY) of 25%. In a two-step labeling protocol, we synthesized the [11C]MeA in acetonitrile in advance to the click step. Using the more soluble Na+/18-crown-6/N3- complex as source of N3-, a much higher trapping efficiency of [11C]MeI in this solvent ensured an almost quantitative conversion of [11C]MeI to [11C]MeA within 5-10 min at room temperature. The [11C]MeA was thereafter reacted with ethynylbenzene at 100 °C yielding 1-[11C]methyl-4-phenyl-1H-1,2,3-triazole in preparative RCY of 60%. As a final proof of applicability, we used 11C-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 Tyr3-octreotate derivative.

The in situ synthesis of [11C]methyl azide and its application in click-chemistry are reported.