Late stage 18F-difluoromethylation of N-heteroaromatics
type: CreativeWork
description: We herein describe a new methodology for the late stage addition of CHF18F to N-heteroaromatics for PET imaging. This methodology proceeds via C-H activation, under flow photoredox conditions. The 18F-difluoromethylation relies on the use of a new 18F-difluoromethylating reagent derived from the Hu’s reagent. This reagent is organic and produces a CHF2 radical under blue LED irradiation, based on previous reported publications. The fluorine-18 labeling of the Hu’s reagent was performed by Agostinho Lemos, in collaboration with the University of Liège (ULG). Meanwhile, the difluoromethylation of N-heteroaromatics typically found in medicinal chemistry programs was first explored in non-radioactive conditions, and then translated in fluorine-18 chemistry. In fluorine-18 chemistry, the reaction proceeds fast (2 minutes), is applicable to a broad range of N-heteroaromatics (benzimidazoles, indoles, pyridines, etc) and drug-like compounds. Furthermore, as demonstrated on Acyclovir, 18F-difluoromethylated compounds were successfully obtained with molar activities suitable for PET imaging (1.2 Ci/µmol), an important criterion for further PET development. Following these studies, the 18F-difluoromethylation protocol was successfully automated on a commercial synthesizer: the AllinOne (AIO) from Trasis. Finally, the application of the 18F-difluoromethylation to the preparation of a novel SV2A PET tracer was performed and shows promising results.
abstract: We herein describe a new methodology for the late stage addition of CHF18F to N-heteroaromatics for PET imaging. This methodology proceeds via C-H activation, under flow photoredox conditions. The 18F-difluoromethylation relies on the use of a new 18F-difluoromethylating reagent derived from the Hu’s reagent. This reagent is organic and produces a CHF2 radical under blue LED irradiation, based on previous reported publications. The fluorine-18 labeling of the Hu’s reagent was performed by Agostinho Lemos, in collaboration with the University of Liège (ULG). Meanwhile, the difluoromethylation of N-heteroaromatics typically found in medicinal chemistry programs was first explored in non-radioactive conditions, and then translated in fluorine-18 chemistry. In fluorine-18 chemistry, the reaction proceeds fast (2 minutes), is applicable to a broad range of N-heteroaromatics (benzimidazoles, indoles, pyridines, etc) and drug-like compounds. Furthermore, as demonstrated on Acyclovir, 18F-difluoromethylated compounds were successfully obtained with molar activities suitable for PET imaging (1.2 Ci/µmol), an important criterion for further PET development. Following these studies, the 18F-difluoromethylation protocol was successfully automated on a commercial synthesizer: the AllinOne (AIO) from Trasis. Finally, the application of the 18F-difluoromethylation to the preparation of a novel SV2A PET tracer was performed and shows promising results.
author: Trump, Laura
language: en
keywords: difluoromethylation, radiochemistry, fluorine-18, flow chemistry, photoredox, Physical, chemical, mathematical & earth Sciences, Chemistry, Physique, chimie, mathématiques & sciences de la terre, Chimie
license: http://purl.org/coar/access_right/c_16ec
date published: 2019-12-13
date modified: 2026-07-24T02:49:39Z
provider: Université de Liège
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: ULiège - Université de Liège