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Title: N, N, N-Trimethyl-5-[(2,3,5,6-tetrafluorophenoxy)carbonyl]pyridin-2-aminium trifluoromethanesulfonate a precursor for the synthesis of 2,3,5,6-tetrafluorophenyl 6-[ 18 F]-fluoronicotinate

Abstract

The synthesis, recrystallization, and X-ray deterimination of N, N, N-trimethyl-5-[(2,3,5,6-tetrafluorophenoxy)carbonyl]pyridin-2-aminium trifluoromethanesulfonate (PyTFP-precursor), C 15H 13F 4N 2O 2 +·CF 3SO 3 -, is described. This triflate salt precursor is required for the synthesis of 2,3,5,6-tetrafluorophenyl 6-[ 18F]-fluoronicotinate ([ 18F]FPyTFP), a prosthetic group used to radiolabel peptides for positron emission tomography (PET), as peptides are increasingly being used as PET-imaging probes in nuclear medicine. Radiolabeling of peptides is typically done using a `prosthetic group', a small synthon to which the radioisotope is attached in the first step, followed by attachment to the peptide in the second step. During the synthesis of the PyTFP-precursor, displacement of a Cl atom with trimethylamine gas and anion replacement with a triflate counter-ion is critical, as incomplete replacement would hinder radioisotopic incorporation of nucleophilic fluorine-18 and result in diminished radiochemical yields. The structural determination of the PyTFP-precursor by X-ray crystallography helped confirm the anion exchange of chloride with triflate.

Authors:
ORCiD logo;
Publication Date:
Research Org.:
Univ. of California, Davis, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1541444
DOE Contract Number:  
SC0008385
Resource Type:
Journal Article
Journal Name:
Acta Crystallographica. Section C, Structural Chemistry (Online)
Additional Journal Information:
Journal Volume: 74; Journal Issue: 5; Journal ID: ISSN 2053-2296
Publisher:
International Union of Crystallography
Country of Publication:
United States
Language:
English
Subject:
Chemistry; Crystallography

Citation Formats

Davis, Ryan A., and Fettinger, James C. N, N, N-Trimethyl-5-[(2,3,5,6-tetrafluorophenoxy)carbonyl]pyridin-2-aminium trifluoromethanesulfonate a precursor for the synthesis of 2,3,5,6-tetrafluorophenyl 6-[ 18 F]-fluoronicotinate. United States: N. p., 2018. Web. doi:10.1107/s2053229618005430.
Davis, Ryan A., & Fettinger, James C. N, N, N-Trimethyl-5-[(2,3,5,6-tetrafluorophenoxy)carbonyl]pyridin-2-aminium trifluoromethanesulfonate a precursor for the synthesis of 2,3,5,6-tetrafluorophenyl 6-[ 18 F]-fluoronicotinate. United States. doi:10.1107/s2053229618005430.
Davis, Ryan A., and Fettinger, James C. Wed . "N, N, N-Trimethyl-5-[(2,3,5,6-tetrafluorophenoxy)carbonyl]pyridin-2-aminium trifluoromethanesulfonate a precursor for the synthesis of 2,3,5,6-tetrafluorophenyl 6-[ 18 F]-fluoronicotinate". United States. doi:10.1107/s2053229618005430.
@article{osti_1541444,
title = {N, N, N-Trimethyl-5-[(2,3,5,6-tetrafluorophenoxy)carbonyl]pyridin-2-aminium trifluoromethanesulfonate a precursor for the synthesis of 2,3,5,6-tetrafluorophenyl 6-[ 18 F]-fluoronicotinate},
author = {Davis, Ryan A. and Fettinger, James C.},
abstractNote = {The synthesis, recrystallization, and X-ray deterimination of N, N,N-trimethyl-5-[(2,3,5,6-tetrafluorophenoxy)carbonyl]pyridin-2-aminium trifluoromethanesulfonate (PyTFP-precursor), C15H13F4N2O2+·CF3SO3-, is described. This triflate salt precursor is required for the synthesis of 2,3,5,6-tetrafluorophenyl 6-[18F]-fluoronicotinate ([18F]FPyTFP), a prosthetic group used to radiolabel peptides for positron emission tomography (PET), as peptides are increasingly being used as PET-imaging probes in nuclear medicine. Radiolabeling of peptides is typically done using a `prosthetic group', a small synthon to which the radioisotope is attached in the first step, followed by attachment to the peptide in the second step. During the synthesis of the PyTFP-precursor, displacement of a Cl atom with trimethylamine gas and anion replacement with a triflate counter-ion is critical, as incomplete replacement would hinder radioisotopic incorporation of nucleophilic fluorine-18 and result in diminished radiochemical yields. The structural determination of the PyTFP-precursor by X-ray crystallography helped confirm the anion exchange of chloride with triflate.},
doi = {10.1107/s2053229618005430},
journal = {Acta Crystallographica. Section C, Structural Chemistry (Online)},
issn = {2053-2296},
number = 5,
volume = 74,
place = {United States},
year = {2018},
month = {4}
}

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