New methods for incorporating no-carrier-added (NCA) fluorine-18 into aryl C-F bonds are of great interest due to the enhanced metabolic stability of [18F]fluoroaryl species in candidate PET radiotracers. Our previous work has demonstrated that diarylselenones and diarylselenoxides can react efficiently with NCA [18F]fluoride ion to give [18F]fluoroarenes. Here we report the use of such hypervalent selenium precursors for the synthesis of [18F]FPEB ([18F]3-fluoro-5-[(pyridin-2-yl)ethynyl]benzonitrile), a selective mGluR5 ligand and useful PET radioligand. A Sonogashira coupling between 3,5-diiodobenzonitrile and 2-ethynylpyridine afforded the iodo analogue of FPEB. Subsequent reaction with diphenyl diselenide provided the phenylselenyl analogue, and oxidation with meta-chloroperbenzoic acid resulted in selenoxide precursor 1. This compound was further oxidized with Oxone to give selenone precursor 2. Both precursors were treated with [18F]F−.K+.K2.2.2 in DMF and microwaved (90 s, 90 W, 150 °C) twice in a 1-mL V-vial, and production of [18F]FPEB was identified by observation of coelution with commercial reference compound in HPLC. Selenoxide 1 produced the desired radioligand in moderate yield (27%), which is comparable to that reported from other precursors, including aryliodonium salts. Additionally, selenone 2 produced [18F]FPEB in much higher yield (88%). The facile production of this radioligand from selenium-based precursors under mild microwave conditions warrants investigation of selenium-based precursors for producing other useful PET radioligands.

Synthesis of [18F]FPEB through radiofluorination of a diarylselenoxide and diarylselenone precursor

2019 Fall National Meeting

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