2-, 3- and 4-[18F]Fluoropyridine by no-carrier-added nucleophilic aromatic substitution with K[18F]F-K222 - a comparative study

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 46; no. 10; pp. 979 - 992
• Main Authors: Karramkam, M., Hinnen, F., Vaufrey, F., Dollé, F.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.09.2003; Wiley
• Subjects: Biological and medical sciences; Chemistry; Contrast media. Radiopharmaceuticals; Exact sciences and technology; fluorine-18; fluoropyridine; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; labellin; Medical sciences; microwaves; nucleophilic aromatic substitution; Organic chemistry; Pharmacology. Drug treatments; Preparations and properties; Fluorine Isotopes; Fluorine 18; Radiolabelling; Microwave; Potassium Fluorides; Nucleophilic substitution; Chemical synthesis; Operating conditions; SNAr mechanism
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.730

Compared to homoaromatic and aliphatic nucleophilic radiofluorinations, only few references can be found in the literature describing nucleophilic substitutions with [18F]fluoride ion of heteroaromatic compounds such as pyridines and only reactions involving fluorination processes at the ortho‐position (2‐position) have been more intensively studied. In the present paper, the scope of the nucleophilic aromatic fluorinations at the meta‐ and para‐position of the pyridine ring with no‐carrier‐added [18F]fluoride ion as its activated K[18F]F‐K222 complex has been evaluated and compared to the nucleophilic aromatic fluorinations at the ortho‐position in this pyridine series. The syntheses of 3‐ and 4‐[18F]fluoropyridines were chosen as model reactions and compared to the radiosynthesis of 2‐[18F]fluoropyridine. The parameters studied include the influence of the position of the leaving group at the pyridine ring, as well as the quantity of the precursor used, the type of activation (conventional heating, microwave irradiation), the solvent, the temperature and the reaction time. Using the corresponding nitro precursor, high yields were obtained at the 2‐position (94% yield) using microwaves (100 W) for 2 min in DMSO. Good yields (up to 72%) were observed at the 4‐position using the same conditions while practically no reaction was observed at the 3‐position. About 60% yield was also obtained at both the 2‐ and 4‐position using the corresponding nitro precursor at 145°C for 10 min in DMSO. Copyright © 2003 John Wiley & Sons, Ltd.