% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@INPROCEEDINGS{Omrane:866645,
author = {Omrane, Aymen and Zlatopolskiy, Boris and Neumaier, Bernd},
title = {2‐[18{F}]{F}luoro‐5‐iodopyridine ([18{F}]{FIP}y): {A}
novel reactive prosthetic group for the fast site specific
radiolabeling via {P}d‐catalyzed cross coupling reactions},
reportid = {FZJ-2019-05724},
year = {2019},
abstract = {Aim: Numerous Pd‐catalyzed cross‐couplings like
Sonogashira, Suzuki‐Miyaura, Heck, and Stille reactions
proved to be valuable tools for the site specific labeling
of biopolymers. The aim of this work was the study of
Pd‐catalyzed cross coupling reactions using [18F]FIPy as
radiolabeled synthon and
2,2′‐(1,2‐phenylene)‐bis‐(4,4‐dimethyl‐4,5‐dihydrooxazole)‐N,N′‐palladium
dichloride (Pd‐BOX‐1) as catalyst. Pd‐BOX‐1
demonstrated exceptional air and moisture stability and
excellent catalytic activity in aqueous reaction media.
MethodsThe direct reaction of 2‐bromo‐5‐iodopyridine
with DABCO followed by anion metathesis using TMSOTf
afforded
1‐(5‐iodopyridin‐2‐yl)‐1,4‐diazabicyclo[2.2.2]octan‐1‐ium
triflate (1) used as precursor for the preparation of
[18F]FIPy. The latter was produced using the
“minimalist” protocol. Accordingly, [18F]fluoride was
eluted from a QMA cartridge with a solution of 1 in MeOH.
MeOH was evaporated at 45°C (250 mbar) within 4 min, DMSO
was added, and the resulting solution was heated affording
[18F]FIPy, which after the purification by SPE was
conjugated to different model compounds by different
Pd‐catalyzed $(1\%$ of Pd‐BOX‐1) cross‐couplings
using aqueous MeCN or DMF as reaction solvent within 10 min.
Results18F– recovery from an anion exchange resin using 1
(3 mg) amounted $>98\%.$ Heating of the resulting
[18F]fluoride onium salt in DMSO at 100°C for 15 min
afforded [18F]FIPy in excellent radiochemical conversions
(RCCs) of 91 ± $3\%.$ [18F]FIPy was isolated in 61 ± $5\%$
radiochemical yield (RCY) and excellent radiochemical purity
(RCP) of $>98\%.$ The subsequent Cu and phosphine free
Pd‐BOX‐1 catalyzed Sonogashira cross‐coupling with
phenylacetylene afforded the corresponding conjugate in an
excellent RCC of $>89\%.$ Furthermore, Suzuki‐Miyaura,
Heck, and Stille reactions with 4‐methylphenyl boronic
acid, methyl acrylate, and trimethyl (phenyl)tin,
respectively, applied as model coupling partners furnished
the corresponding radiofluorinated conjugates in RCCs of
$85–98\%.$ Conclusion[18F]FIPy is a valuable radiolabeled
prosthetic group easily accessible using the
“minimalist” approach. Various Pd‐BOX‐1‐catalyzed
cross coupling reactions with [18F]FIPy is a versatile
procedure for a fast, high‐yielding, and site specific
radiolabeling under relatively mild conditions.},
month = {May},
date = {2019-05-26},
organization = {The 23rd International Symposium on
Radiopharmaceutical Sciences, Beijing
(China), 26 May 2019 - 31 May 2019},
subtyp = {After Call},
cin = {INM-5},
cid = {I:(DE-Juel1)INM-5-20090406},
pnm = {573 - Neuroimaging (POF3-573)},
pid = {G:(DE-HGF)POF3-573},
typ = {PUB:(DE-HGF)6},
url = {https://juser.fz-juelich.de/record/866645},
}