title: Synthesis of meta-substituted [(18)F]3-fluoro-4-aminopyridine via direct radiofluorination of pyridine N-oxides.
abstract: Due to their electron-rich aromatic structure, nucleophilic (radio)fluorination of pyridines is challenging, especially at the meta position. In this paper, we describe the first example of direct fluorination of a pyridine N-oxide to produce a meta fluorinated pyridine. Specifically, fluorination of 3-bromo-4-nitropyridine N-oxide produced in several minutes 3-fluoro-4-nitropyridine N-oxide in moderate yield at room temperature. This intermediate compound was later converted to 3-fluoro-4-aminopyridine easily by catalytic hydrogenation. Furthermore, this approach was successfully applied for labeling with fluorine-18. The use of pyridine N-oxides for the preparation of fluoropyridines is unprecedented in the chemical literature and has the potential to offer a new way for the synthesis of these important structures in pharmaceuticals and radiopharmaceuticals.
authors.affiliation: Department of Neurology, The University of Chicago, Chicago, IL 60637, USA. brugarolas@uchicago.edu.
authors.forename: P
authors.initials: P
authors.lastname: Brugarolas
authors.forename: R
authors.initials: R
authors.lastname: Freifelder
authors.forename: S-H
authors.initials: SH
authors.lastname: Cheng
authors.forename: O
authors.initials: O
authors.lastname: DeJesus
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis* / Q000737:chemistry; D005462:Fluorine Radioisotopes; D054879:Halogenation; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry*
chemical_list: D000631:Aminopyridines; D005462:Fluorine Radioisotopes; D011725:Pyridines; C013229:pyridine N-oxide; C000615276:Fluorine-18