Late‐Stage Isotopic Carbon Labeling of Pharmaceutically Relevant Cyclic Ureas Directly from CO<sub>2</sub>

Vecchio, Antonio Del; Caillé, Fabien; Chevalier, Arnaud; Loreau, Olivier; Horkka, Kaisa; Halldin, Christer; Schou, Magnus; Camus, Nathalie; Kessler, Pascal; Kühnast, Bertrand; Taran, Frédéric

doi:10.1002/ange.201804838

Cited by 15 publications

(12 citation statements)

References 55 publications

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“…These drawbacks impede the broader application of [ 11 C]CO 2 for synthesizing highly functionalized molecules. To expand the utility of [ 11 C]CO 2 for the synthesis of PET tracers with diverse structures, including multiple functional groups, researchers have recently reported on both the incorporation of [ 11 C]CO 2 into molecules under milder conditions, and the introduction of 11 C to specific positions that are not easily achieved using other secondary radiosynthons [4][5][6][7][8][9][10] . Despite such developments, the method of directly incorporating [ 11 C]CO 2 for synthesis of 11 C-labeled radiotracers remains sorely lacking in the field of PET chemistry.…”

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confidence: 99%

A general 11C-labeling approach enabled by fluoride-mediated desilylation of organosilanes

Qü

Babich

et al. 2020

Nat Commun

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Carbon-11 (11C) is one of the most ideal positron emitters for labeling bioactive molecules for molecular imaging studies. The lack of convenient and fast incorporation methods to introduce 11C into organic molecules often hampers the use of this radioisotope. Here, a fluoride-mediated desilylation (FMDS) 11C-labeling approach is reported. This method relies on thermodynamically favored Si-F bond formation to generate a carbanion, therefore enabling the highly efficient and speedy incorporation of [11C]CO2 and [11C]CH3I into molecules with diversified structures. It provides facile and rapid access to 11C-labeled compounds with carbon-11 attached at various hybridized carbons as well as oxygen, sulfur and nitrogen atoms with broad functional group tolerance. The exemplified syntheses of several biologically and clinically important radiotracers illustrates the potentials of this methodology.

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confidence: 99%

A general 11C-labeling approach enabled by fluoride-mediated desilylation of organosilanes

Qü

Babich

et al. 2020

Nat Commun

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“…Furthermore, N,N'-dimethyl o-diaminobenzene gave the cyclization product [ 11 C]5 in 61 AE 5 % yield. This labeled compound had been inaccessible through the azide-based [ 11 C]CO 2 -fixation method of Del Vecchio et al [19] and only accessible in low yields using a dehydration strategy with phosphines and diazacarboxylates by the method of Horkka et al [20] Ureas [ 11 C]6 and [ 11 C]7, bearing electron-withdrawing substituents, were labeled in 49 AE 12 % and 82 AE 4 % yields, respectively, thereby further demonstrating the strong reactivity of [27] m-opioid antagonists, [28] as well as the antipsychotics pimozide [10] and benperidol [29] ). We selected three PET radiotracers to test the utility of [ 11 C]COF 2 for labeling more complex and useful structures.…”

Section: Communicationsmentioning

confidence: 99%

[¹¹C]Carbonyl Difluoride—a New and Highly Efficient [¹¹C]Carbonyl Group Transfer Agent

Jakobsson

Telu

et al. 2020

Angew Chem Int Ed

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Herein, the synthesis and use of [ 11 C]carbonyl difluoride for labeling heterocycles with [ 11 C]carbonyl groups in high molar activity is described. A very mild single-pass gasphase conversion of [ 11 C]carbon monoxide into [ 11 C]carbonyl difluoride over silver(II) fluoride provides easy access to this new synthon in robust quantitative yield for labeling a broad range of cyclic substrates, for example, imidazolidin-2-ones, thiazolidin-2-ones, and oxazolidin-2-ones. Labeling reactions may utilize close-to-stoichiometric precursor quantities and short reaction times at room temperature in a wide range of solvents while also showing high water tolerability. The overall radiosynthesis protocol is both simple and reproducible. The required apparatus can be constructed from widely available parts and is therefore well suited to be automated for PET radiotracer production. We foresee that this straightforward method will gain wide acceptance for PET radiotracer syntheses across the radiochemistry community.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

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“…Recently, we used a click‐chemistry‐inspired approach to label cyclic ureas by applying the Staudinger reaction to o ‐azidoanilines . In our search for alternative methods for such transformations, we turned our attention to o‐ phenylenediamines as substrates.…”

Section: Introductionmentioning

confidence: 99%

Rapid and Efficient Synthesis of ¹¹C‐Labeled Benzimidazolones Using [¹¹C]Carbon Dioxide

et al. 2019

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[11C]Carbon dioxide is an attractive synthon for the labeling of positron emission tomography (PET) tracers for subsequent use in biomedical research and drug development. In this study, [11C]CO2 was used for direct 11C‐labeling of a set of cyclic aromatic ureas starting from their corresponding ortho‐phenylenediamines, BEMP (2‐tert‐butylimino‐2‐diethylamino‐1,3‐dimethylperhydro‐1,3,2‐diazaphosphorine) as fixation base, and Mitsunobu reagents (DBAD, nBu3P) for the intramolecular cyclization. The procedure is rapid (6 minutes total synthesis time), mild (proceeds at room temperature) and provided a set of 11C‐benzimidazolones in good to excellent radiochemical yields. As a final testament to the utility of this method, the beta‐adrenoceptor PET ligand [11C]CGP12177, was successfully prepared using the optimized conditions.

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Late‐Stage Isotopic Carbon Labeling of Pharmaceutically Relevant Cyclic Ureas Directly from CO₂

Cited by 15 publications

References 55 publications

A general 11C-labeling approach enabled by fluoride-mediated desilylation of organosilanes

A general 11C-labeling approach enabled by fluoride-mediated desilylation of organosilanes

[¹¹C]Carbonyl Difluoride—a New and Highly Efficient [¹¹C]Carbonyl Group Transfer Agent

Rapid and Efficient Synthesis of ¹¹C‐Labeled Benzimidazolones Using [¹¹C]Carbon Dioxide

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Late‐Stage Isotopic Carbon Labeling of Pharmaceutically Relevant Cyclic Ureas Directly from CO2

Cited by 15 publications

References 55 publications

A general 11C-labeling approach enabled by fluoride-mediated desilylation of organosilanes

A general 11C-labeling approach enabled by fluoride-mediated desilylation of organosilanes

[11C]Carbonyl Difluoride—a New and Highly Efficient [11C]Carbonyl Group Transfer Agent

Rapid and Efficient Synthesis of 11C‐Labeled Benzimidazolones Using [11C]Carbon Dioxide

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Product

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About

Late‐Stage Isotopic Carbon Labeling of Pharmaceutically Relevant Cyclic Ureas Directly from CO₂

[¹¹C]Carbonyl Difluoride—a New and Highly Efficient [¹¹C]Carbonyl Group Transfer Agent

Rapid and Efficient Synthesis of ¹¹C‐Labeled Benzimidazolones Using [¹¹C]Carbon Dioxide