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Access to 18 F ‐labelled isoxazoles by ruthenium‐promoted 1,3‐dipolar cycloaddition of 4‐[ 18 F ]fluoro‐ N ‐hydroxybenzimidoyl chloride with alkynes
Author(s) -
Roscales Silvia,
Kniess Torsten
Publication year - 2019
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3708
Subject(s) - chemistry , cycloaddition , synthon , nitrile , radiosynthesis , medicinal chemistry , chloride , benzene , yield (engineering) , organic chemistry , catalysis , microbiology and biotechnology , in vivo , biology , materials science , metallurgy
4‐[ 18 F]Fluoro‐ N ‐hydroxybenzimidoyl chloride ( 18 FBIC), an 18 F‐labelled aromatic nitrile oxide, was developed as building block for Ru‐promoted 1,3‐dipolar cycloaddition with alkynes. 18 FBIC is obtained in a one‐pot synthesis in up to 84% radiochemical yield (RCY) starting from [ 18 F]fluoride with 4‐[ 18 F]fluorobenzaldehyde ( 18 FBA) and 4‐[ 18 F]fluorobenzaldehyde oxime ( 18 FBAO) as intermediates, by reaction of 18 FBAO with N ‐chlorosuccinimide (NCS). 18 FBIC was found to be a suitable and stable synthon to give access to 18 F‐labelled 3,4‐diarylsubstituted isoxazoles by [Cp*RuCl(cod)]‐catalysed 1,3‐dipolar cycloaddition with various alkynes. So the radiosynthesis of a fluorine‐18–labelled COX‐2 inhibitor [ 18 F] 1b , a close derivative of valdecoxib, was performed with 18 FBIC and 1‐ethynyl‐4‐(methylsulfonyl)benzene, providing [ 18 F] 1b in up to 40% RCY after purification in 85 minutes. The application of 18 FBIC as a building block in the synthesis of 18 F‐labelled heterocycles will generally extend the portfolio of available PET radiotracers.