Expedient Access to 18F-Fluoroheteroarenes via Deaminative Radiofluorination of Aniline-Derived Pyridinium Salts

Joseph Ford; Sebastiano Ortalli; Zijun Chen; Jeroen B.I. Sap; Matthew Tredwell; Véronique Gouverneur

doi:10.1002/anie.202404945

Expedient Access to ¹⁸F-Fluoroheteroarenes via Deaminative Radiofluorination of Aniline-Derived Pyridinium Salts

Joseph Ford
, Sebastiano Ortalli
, Zijun Chen
, Jeroen B.I. Sap
, Matthew Tredwell
, Véronique Gouverneur

University of Oxford
Cardiff University School of Medicine
Cardiff University

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Herein, we disclose that pyridinium salts derived from abundant (hetero)anilines represent a novel precursor class for nucleophilic aromatic substitution reactions with [¹⁸F]fluoride. The value of this new ¹⁸F-fluorodeamination is demonstrated with the synthesis of over 30 structurally diverse and complex heteroaryl ¹⁸F-fluorides, several derived from scaffolds that were yet to be labelled with fluorine-18. The protocol tolerates heteroarenes and functionalities commonly found in drug discovery libraries, and is amenable to scale-up and automation on a commercial radiosynthesiser.

Original language	English
Article number	e202404945
Journal	Angewandte Chemie - International Edition
Volume	63
Issue number	26
DOIs	https://doi.org/10.1002/anie.202404945
State	Published - 21 Jun 2024
Externally published	Yes

Keywords

Fluorine
Heterocycles
Nucleophilic substitution
Radiochemistry
Radiopharmaceuticals

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10.1002/anie.202404945

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title = "Expedient Access to 18F-Fluoroheteroarenes via Deaminative Radiofluorination of Aniline-Derived Pyridinium Salts",

abstract = "Herein, we disclose that pyridinium salts derived from abundant (hetero)anilines represent a novel precursor class for nucleophilic aromatic substitution reactions with [18F]fluoride. The value of this new 18F-fluorodeamination is demonstrated with the synthesis of over 30 structurally diverse and complex heteroaryl 18F-fluorides, several derived from scaffolds that were yet to be labelled with fluorine-18. The protocol tolerates heteroarenes and functionalities commonly found in drug discovery libraries, and is amenable to scale-up and automation on a commercial radiosynthesiser.",

keywords = "Fluorine, Heterocycles, Nucleophilic substitution, Radiochemistry, Radiopharmaceuticals",

author = "Joseph Ford and Sebastiano Ortalli and Zijun Chen and Sap, \{Jeroen B.I.\} and Matthew Tredwell and V{\'e}ronique Gouverneur",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.",

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doi = "10.1002/anie.202404945",

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T1 - Expedient Access to 18F-Fluoroheteroarenes via Deaminative Radiofluorination of Aniline-Derived Pyridinium Salts

AU - Ford, Joseph

AU - Ortalli, Sebastiano

AU - Chen, Zijun

AU - Sap, Jeroen B.I.

AU - Tredwell, Matthew

AU - Gouverneur, Véronique

PY - 2024/6/21

Y1 - 2024/6/21

N2 - Herein, we disclose that pyridinium salts derived from abundant (hetero)anilines represent a novel precursor class for nucleophilic aromatic substitution reactions with [18F]fluoride. The value of this new 18F-fluorodeamination is demonstrated with the synthesis of over 30 structurally diverse and complex heteroaryl 18F-fluorides, several derived from scaffolds that were yet to be labelled with fluorine-18. The protocol tolerates heteroarenes and functionalities commonly found in drug discovery libraries, and is amenable to scale-up and automation on a commercial radiosynthesiser.

AB - Herein, we disclose that pyridinium salts derived from abundant (hetero)anilines represent a novel precursor class for nucleophilic aromatic substitution reactions with [18F]fluoride. The value of this new 18F-fluorodeamination is demonstrated with the synthesis of over 30 structurally diverse and complex heteroaryl 18F-fluorides, several derived from scaffolds that were yet to be labelled with fluorine-18. The protocol tolerates heteroarenes and functionalities commonly found in drug discovery libraries, and is amenable to scale-up and automation on a commercial radiosynthesiser.

KW - Fluorine

KW - Heterocycles

KW - Nucleophilic substitution

KW - Radiochemistry

KW - Radiopharmaceuticals

UR - https://www.scopus.com/pages/publications/85194133272

U2 - 10.1002/anie.202404945

DO - 10.1002/anie.202404945

M3 - Article

C2 - 38624193

AN - SCOPUS:85194133272

SN - 1433-7851

VL - 63

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 26

M1 - e202404945

ER -

Expedient Access to ¹⁸F-Fluoroheteroarenes via Deaminative Radiofluorination of Aniline-Derived Pyridinium Salts

Abstract

Keywords

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