Late‐Stage 18F‐Difluoromethyl Labeling of N‐Heteroaromatics with High Molar Activity for PET Imaging

Despite a growing interest in CHF2 in medicinal chemistry, there is a lack of efficient methods for the insertion of CHF18F into druglike compounds. Herein described is a photoredox flow reaction for 18F‐difluoromethylation of N‐heteroaromatics that are widely used in medicinal chemistry. Following...

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Published inAngewandte Chemie International Edition Vol. 58; no. 37; pp. 13149 - 13154
Main Authors Trump, Laura, Lemos, Agostinho, Lallemand, Bénédicte, Pasau, Patrick, Mercier, Joël, Lemaire, Christian, Luxen, André, Genicot, Christophe
Format Journal Article
LanguageEnglish
Published Weinheim Wiley Subscription Services, Inc 09.09.2019
John Wiley and Sons Inc
EditionInternational ed. in English
Subjects
Biological activity
Chemical synthesis
C−H activation
flow chemistry
fluorine
Fluorine isotopes
In vivo methods and tests
Organic chemistry
Pharmaceutical sciences
photochemistry
Positron emission
radiochemistry
Reagents
Substrates
Tomography
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Summary:Despite a growing interest in CHF2 in medicinal chemistry, there is a lack of efficient methods for the insertion of CHF18F into druglike compounds. Herein described is a photoredox flow reaction for 18F‐difluoromethylation of N‐heteroaromatics that are widely used in medicinal chemistry. Following the two‐step synthesis for a new 18F‐difluoromethylation reagent, the photoredox reaction is completed within two minutes and proceeds by C−H activation, circumventing the need for pre‐functionalization of the substrate. The method is operationally simple and affords straightforward access to radiolabeled N‐heteroaromatics with high molar activity suitable for biological in vivo studies and clinical application. Make a trace: A new flow photoredox methodology allows the 18F‐difluoromethylation of heteroaromatics by C−H activation. The method is applicable to a wide range of heteroaromatics and can be used for the preparation of radiotracers with high molar activities that are suitable for positron emission tomography studies.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201907488