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

Abstract

SummaryCompared to homoaromatic and aliphatic nucleophilic radiofluorinations, only few references can be found in the literature describing nucleophilic substitutions with 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

[18F]FPyKYNE, a fluoropyridine‐based alkyne reagent designed for the fluorine‐18 labelling of macromolecules using click chemistry

“…47,48 All three precursors for labelling synthesized above (derivatives 8, 9 and 11) were tested within a range of 10-30 mmol engaged per run. DMSO as the solvent and 1651C as the temperature were selected for these reactions based on literature, 49,50 whereas different times of reaction were studied. A DMSO solution (600 mL) containing the precursor for labelling (8, 9 or 11) was transferred to 300-600 mCi of the dried K[ For each time point, TLC analyses (SiO 2 , EtOAc, see the Experimental) showed only one radioactive peak (R f : 0.75), comigrating with FPyKYNE (1), besides unreacted […”

Synthesis of fluorine‐18‐labelled 5‐ and 6‐fluoro‐2‐pyridinamine

“…The first step consisted of no-carrier-added nucleophilic aromatic substitution of commercially available halogen-substituted 2-pyridinecarboxamide or 2-pyridinecarbonitrile derivatives with K[ ]fluoropyridine (70-90%), whereas no reaction was observed for substitution at the meta-position. 3 In contrast to ortho-and para-substitution, nucleophilic [ 18 F]fluorination at the meta-position requires an additional electronwithdrawing substituent in the pyridine ring. To our knowledge, only one example of meta-[…”

Synthese von 11C‐, 18F‐, 15O‐ und 13N‐Radiotracern für die Positronenemissionstomographie

“…Eine potenziell wichtige Anwendung der palladiumkatalysierten Kreuzkupplung, [195,196] in nucleophilen 18 F-Substitutionen hat sich als extrem nützliche Alternative zur Synthese einer Reihe einfacher 18 F-Fluorarene erwiesen, die durch andere konventionelle Verfahren nicht zugänglich sind. Eine kürzlich veröffentlichte Studie [197] vergleicht gebräuchliche Methoden für die einstufige Synthese von 1-Brom- [203] Eine meta-Substitution ist möglich, wenn elektronenziehende Substituenten in ortho-oder para-Stellung vorliegen und die meta-Abgangsgruppe aktivieren. [204] Heteroaromatische nucleophile 18 FSubstitutionen an der ortho-Position zur Pyridylgruppe sind die effizienteste Route zu 18 F-markierten Fluorpyridylen mit […”