From [11C]CO2 to [11C]amides: a rapid one-pot synthesis via the Mitsunobu reaction

Bongarzone, Salvatore; Runser, A.; Taddei, Carlotta; Dheere, Abdul Karim Haji; Gee, Antony D.

doi:10.1039/c7cc01407d

Cited by 23 publications

(31 citation statements)

References 22 publications

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“…Two novel methodologies based on [ 11 C]CO 2 trapping in the presence of BEMP and subsequent addition of Mitsunobu reagents have been developed, Scheme (A and B) to expand the range of functionalised [ 11 C]ureas . A similar approach has been also recently discovered for the synthesis of [ 11 C]amides via rapid addition of Grignard regents after Mitsunobu reaction, Scheme (C) . These direct [ 11 C]CO 2 fixation methodologies are attractive alternatives for the synthesis of functionalised [ 11 C]ureas and [ 11 C]amides compared with the [ 11 C]COCl 2 ‐based methods.…”

Section: Introductionsupporting

confidence: 77%

Recent progress in [¹¹C]carbon dioxide ([¹¹C]CO₂) and [¹¹C]carbon monoxide ([¹¹C]CO) chemistry

Taddei

Gee

2018

Labelled Comp Radiopharmac

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[ 11 C]Carbon dioxide ([ 11 C]CO 2 ) and [ 11 C]carbon monoxide ([ 11 C]CO) are 2 attractive precursors for labelling the carbonyl position (C═O) in a vast range of functionalised molecules (eg, ureas, amides, and carboxylic acids). The development of radiosynthetic methods to produce functionalised 11 C‐labelled compounds is required to enhance the radiotracers available for positron emission tomography, molecular, and medical imaging applications. Following a brief summary of secondary 11 C‐precursor production and uses, the review focuses on recent progress with direct 11 C‐carboxylation routes with [ 11 C]CO 2 and 11 C‐carbonylation with [ 11 C]CO. Novel approaches to generate [ 11 C]CO using CO‐releasing molecules (CO‐RMs), such as silacarboxylic acids and disilanes, applied to radiochemistry are described and compared with standard [ 11 C]CO production methods. These innovative [ 11 C]CO synthesis strategies represent efficient and reliable [ 11 C]CO production processes, enabling the widespread use of [ 11 C]CO chemistry within the wider radiochemistry community.

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Section: Introductionsupporting

confidence: 77%

Recent progress in [¹¹C]carbon dioxide ([¹¹C]CO₂) and [¹¹C]carbon monoxide ([¹¹C]CO) chemistry

Taddei

Gee

2018

Labelled Comp Radiopharmac

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“…Using the in‐loop flow radiosynthesis setup, the radio‐HPLC of the crude solution showed a radiochemical purity of 82.6 ± 3.3%. This coupled with the overall T loop of 78.3 ± 3.6% led to a decay‐corrected nonisolated radiochemical yield (RCY) of 72.3 ± 5.1% (n = 3) for the synthesis of N , N ′‐[ 11 C]dibenzylurea, in 3 minutes from EOB, with a molar radioactivity of 0.72 ± 0.17 GBq/μmol (for 300‐350 MBq initial [ 11 C]CO 2 ; other work in the group has demonstrated that this molar radioactivity would be expected to increase towards 60 to 70 GBq/μmol for an initial 30 GBq [ 11 C]CO 2 production, which is consistent with the molar radioactivities obtained for other clinical 11 C‐labelled radiotracers within our institution) . This therefore presents a reproducible, rapid, and high‐yielding synthesis of a carbon‐11–labelled urea product directly from [ 11 C]CO 2 .…”

Section: Resultsmentioning

confidence: 99%

“…N , N ′‐[ 11 C]dibenzylurea was obtained with high nonisolated RCYs (approximately 72%), comparable to those previously reported in‐vial (approximately 82%), within 3 minutes from EOB (recently presented in abstract form at the International Symposium on Radiopharmaceutical Sciences, ISRS, Dresden, 14‐19 May 2017) . This novel methodology has demonstrated the potential for direct‐from‐cyclotron in‐loop [ 11 C]CO 2 fixation and has demonstrated that this can be used as part of a more complex synthesis (eg, amides and carbamates) . The speed of the reaction (3 min from EOB) and the cheap/disposable ETFE tubing setup (ideal for GMP production) mean that this method should be suitable for further applications in the direct trapping/fixation reactions of [ 11 C]CO 2 .…”

Section: Discussionmentioning

confidence: 99%

In‐loop flow [¹¹C]CO₂ fixation and radiosynthesis of N,N′‐[¹¹C]dibenzylurea

Downey

Bongarzone

Hader

et al. 2017

Labelled Comp Radiopharmac

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Cyclotron‐produced carbon‐11 is a highly valuable radionuclide for the production of positron emission tomography (PET) radiotracers. It is typically produced as relatively unreactive carbon‐11 carbon dioxide ([11C]CO2), which is most commonly converted into a more reactive precursor for synthesis of PET radiotracers.The development of [11C]CO2 fixation methods has more recently enabled the direct radiolabelling of a diverse array of structures directly from [11C]CO2, and the advantages afforded by the use of a loop‐based system used in 11C‐methylation and 11C‐carboxylation reactions inspired us to apply the [11C]CO2 fixation “in‐loop.” In this work, we developed and investigated a new ethylene tetrafluoroethylene (ETFE) loop‐based [11C]CO2 fixation method, enabling the fast and efficient, direct‐from‐cyclotron, in‐loop trapping of [11C]CO2 using mixed DBU/amine solutions. An optimised protocol was integrated into a proof‐of‐concept in‐loop flow radiosynthesis of N,N′‐[11C]dibenzylurea. This reaction exhibited an average 78% trapping efficiency and a crude radiochemical purity of 83% (determined by radio‐HPLC), giving an overall nonisolated radiochemical yield of 72% (decay‐corrected) within just 3 minutes from end of bombardment.This proof‐of‐concept reaction has demonstrated that efficient [11C]CO2 fixation can be achieved in a low‐volume (150 μL) ETFE loop and that this can be easily integrated into a rapid in‐loop flow radiosynthesis of carbon‐11–labelled products.This new in‐loop methodology will allow fast radiolabelling reactions to be performed using cheap/disposable ETFE tubing setup (ideal for good manufacturing practice production) thereby contributing to the widespread usage of [11C]CO2 trapping/fixation reactions for the production of PET radiotracers.

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“…Three compounds containing the acetyl moiety were selected, lacosamide, melatonin and acecainide. The corresponding amine precursor was labelled by using the standard conditions to give [ 11 C]lacosamide in 52 ± 2 % RCY, [ 11 C]melatonin in 55 ± 1 % RCY, and [ 11 C]acecainide in 44 ± 1 % RCY (Scheme ). In the case of the [ 11 C]acecainide amine precursor, the corresponding HCl salt was used together with 2 equiv.…”

Section: Resultsmentioning

confidence: 99%

¹¹C‐Acetylation of Amines with [¹¹C]Methyl Iodide with Bis(cyclopentadienyldicarbonyliron) as the CO Source

Dahl¹,

Nordeman

2017

Eur J Org Chem

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We describe herein a novel approach for the direct 11C‐acetylation of amines. The carbonylative protocol is palladium‐mediated, uses bis(cyclopentadienyldicarbonyliron) as the CO source, and [11C]methyl iodide or [11C]methyl iodide‐D3 as a radioactive precursor. A set of functionalized primary and secondary amines was 11C‐labelled in radiochemical yields ranging from 7–85 %. The potential use of this method for positron emission tomography radiotracer production was additionally demonstrated by the radiosynthesis of [11C]lacosamide, [11C]melatonine, and [11C]acecainide in 44–55 % RCY.

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From [¹¹C]CO₂ to [¹¹C]amides: a rapid one-pot synthesis via the Mitsunobu reaction

Abstract: Radiosynthesis of [11C]amides via the Mitsunobu reaction.

Cited by 23 publications

References 22 publications

Recent progress in [¹¹C]carbon dioxide ([¹¹C]CO₂) and [¹¹C]carbon monoxide ([¹¹C]CO) chemistry

Recent progress in [¹¹C]carbon dioxide ([¹¹C]CO₂) and [¹¹C]carbon monoxide ([¹¹C]CO) chemistry

In‐loop flow [¹¹C]CO₂ fixation and radiosynthesis of N,N′‐[¹¹C]dibenzylurea

¹¹C‐Acetylation of Amines with [¹¹C]Methyl Iodide with Bis(cyclopentadienyldicarbonyliron) as the CO Source

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From [11C]CO2 to [11C]amides: a rapid one-pot synthesis via the Mitsunobu reaction

Abstract: Radiosynthesis of [11C]amides via the Mitsunobu reaction.

Cited by 23 publications

References 22 publications

Recent progress in [11C]carbon dioxide ([11C]CO2) and [11C]carbon monoxide ([11C]CO) chemistry

Recent progress in [11C]carbon dioxide ([11C]CO2) and [11C]carbon monoxide ([11C]CO) chemistry

In‐loop flow [11C]CO2 fixation and radiosynthesis of N,N′‐[11C]dibenzylurea

11C‐Acetylation of Amines with [11C]Methyl Iodide with Bis(cyclopentadienyldicarbonyliron) as the CO Source

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From [¹¹C]CO₂ to [¹¹C]amides: a rapid one-pot synthesis via the Mitsunobu reaction

Recent progress in [¹¹C]carbon dioxide ([¹¹C]CO₂) and [¹¹C]carbon monoxide ([¹¹C]CO) chemistry

Recent progress in [¹¹C]carbon dioxide ([¹¹C]CO₂) and [¹¹C]carbon monoxide ([¹¹C]CO) chemistry

In‐loop flow [¹¹C]CO₂ fixation and radiosynthesis of N,N′‐[¹¹C]dibenzylurea

¹¹C‐Acetylation of Amines with [¹¹C]Methyl Iodide with Bis(cyclopentadienyldicarbonyliron) as the CO Source