Synthesis of fluorine-18 labelled 1-fluoro-2-propanamine via ring-opening of an acyl-aziridine with fluoride: A new synthon for positron emission tomography

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Erik M. van Oosten, erik.vanoosten@utoronto.ca1, Nonik Zadikian, nune.zadikian@gmail.com1, Karin A. Stephenson, karin.stephenson@camhpet.ca2, Alan A. Wilson, alan.wilson@camhpet.ca2, Andrei K. Yudin, ayudin@chem.utoronto.ca1, Jeffrey H. Meyer, jeff.meyer@camhpet.ca2, Sylvain Houle2, and Neil Vasdev, neil.vasdev@camhpet.ca2. (1) Department of Chemistry, University of Toronto, 80 St. George St, Toronto, ON M5S 3H6, Canada, (2) PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada
The present work reports the first synthesis of fluorine-18 (18F, half-life = 109.7 min) labelled 1-fluoro-2-propanamine ([18F]fluoro-isopropylamine). Nucleophilic ring-opening of a benzyloxycarbonyl (CBz)-activated aziridine with fluoride was demonstrated. CBz-N-2-methylaziridine was reacted with 18F-labelled potassium cryptand fluoride for 20 min in DMSO at 75 °C to generate the ring-opened product, CBz-N-fluoroisopropylamine (40% conversion from starting [18F]-activity; n>25). Following solid-phase extraction, the CBz-group was quantitatively removed by catalytic hydrogenation with Pd-C in methanol or acetonitrile. [18F]fluoro-isopropylamine was directly used in a model reaction with benzoyl chloride to prepare the respective benzamide (67% conversion from [18F]fluoro-isopropylamine), and in an epoxide ring-opening reaction to synthesize (S)-[18F]-fluoro-Exaprolol, a novel radiopharmaceutical for imaging ß-adrenergic receptors. Both of the above-mentioned reactions are conducted in one-pot with an end of synthesis time of 2 hours (ca. 1 half-life). This 18F-analog of isopropylamine is a synthetically versatile reagent for preparing radiopharmaceuticals for medical imaging with positron emission tomography.