Development, Optimization, and Scope of the Radiosynthesis of 3/5-[ 18 F]Fluoropyridines from Readily Prepared Aryl(pyridinyl) Iodonium Salts: The Importance of TEMPO and K 2 CO 3

Mathilde Pauton (1, 2) , Catherine Aubert (2) , Guillaume Bluet (2) , Florence Gruss-Leleu (2) , Sébastien Roy (2) , Cécile Perrio (1)

1 ISTCT - Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales
2 Sanofi [Vitry-sur-Seine]

A robust process for the radiosynthesis of 3/5-[18F]fluoropyridines has been developed by radiofluorination of iodonium triflates using K18F/K2CO3/K222 complex in the presence of TEMPO. Both electronically deficient and enriched iodonium salts were readily obtained from the corresponding 3/5-iodopyridines and afforded the corresponding 3/5-[18F]fluoropyridines in 6–78% yields. The concentrations of K2CO3 and TEMPO were found to be crucial for the radiofluorination efficiency. The process was validated using two automated systems for the 18F-radiolabeling of 2-chloro and 2-carboxamido-5-fluoropyridines carried out in 10–20% yields.

Keywords: Iodonium triflate; Radiolabeling; Radiofluorination; Ffluorine-18; 3-fluoropyridine

Domains: Chemical Sciences

Mathilde Pauton, Catherine Aubert, Guillaume Bluet, Florence Gruss-Leleu, Sébastien Roy, et al.. Development, Optimization, and Scope of the Radiosynthesis of 3/5-[ 18 F]Fluoropyridines from Readily Prepared Aryl(pyridinyl) Iodonium Salts: The Importance of TEMPO and K 2 CO 3. Organic Process Research and Development, 2019, 23 (5), pp.900-911. ⟨10.1021/acs.oprd.9b00021⟩. ⟨hal-02110378⟩