229175-16-0

Upstream product

• 10456-04-9 11C-carbon monooxide 
• 100-46-9 benzylamine 
• 67-56-1 methanol 
• 1267658-53-6 C₇⁽¹¹⁾CH₇NO 
• 124-40-3 dimethyl amine 
• 591-50-4 iodobenzene 
• 10375-59-4 [11C]carbon dioxide 
• 111-92-2 dibutylamine 
• 110-89-4 piperidine 
• 103-67-3 benzyl-methyl-amine 
• 2620-50-0 1,3-benzodioxol-5-ylmethyl amine 
• 108-91-8 cyclohexylamine 
• 75-31-0 isopropylamine 

Relevant academic research and scientific papers

Copper(i) scorpionate complexes and their application in palladium-mediated [11C]carbonylation reactions

Solutions of copper(i) tris(pyrazolyl)borate complexes have been used to greatly improve the solubility of [11C]carbon monoxide, enabling it to be used in low-pressure, 'one-pot' palladium-mediated carbonylation reactions to form 11C

Broad Scope and High-Yield Access to Unsymmetrical Acyclic [11C]Ureas for Biomedical Imaging from [11C]Carbonyl Difluoride

Effective methods are needed for labelling acyclic ureas with carbon-11 (t1/2=20.4 min) as potential radiotracers for biomedical imaging with positron emission tomography (PET). Herein, we describe the rapid and high-yield syntheses of unsymmet

Synthesis and pharmacokinetic study of a 11C-labeled cholesterol 24-hydroxylase inhibitor using ‘in-loop’ [11C]CO2 fixation method

Cholesterol 24-hydroxylase, also known as CYP46A1 (EC 1.14.13.98), is a monooxygenase and a member of the cytochrome P450 family. CYP46A1 is specifically expressed in the brain where it controls cholesterol elimination by producing 24S-hydroxylcholesterol (24-HC) as the major metabolite. Modulation of CYP46A1 activity may affect Aβ deposition and p-tau accumulation by changing 24-HC formation, which thereafter serves as potential therapeutic pathway for Alzheimer's disease. In this work, we showcase the efficient synthesis and preliminary pharmacokinetic evaluation of a novel cholesterol 24-hydroxylase inhibitor 1 for use in positron emission tomography.

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

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.

Recent applications of a single quadrupole mass spectrometer in 11C, 18F and radiometal chemistry

Mass spectrometry (MS) has longstanding applications in radiochemistry laboratories, stemming from carbon-dating. However, research on the development of radiotracers for molecular imaging with either positron emission tomography (PET) or single photon emission computed tomography has yet to take full advantage of MS. This inertia has been attributed to the relatively low concentrations of radiopharmaceutical formulations and lack of access to the required MS equipment due to the high costs for purchase and maintenance of specialized MS systems. To date, single quadrupole (SQ)-MS coupled to liquid chromatography (LC) systems is the main form of MS that has been used in radiochemistry laboratories. These LC–MS systems are primarily used for assessing the chemical purity of radiolabeling precursor or standard molecules but also have applications in the determination of metabolites. Herein, we highlight personal experiences using a compact SQ-MS in our PET radiochemistry laboratories, to monitor the small amounts of carrier observed in most radiotracer preparations, even at high molar activities. The use of a SQ-MS in the observation of the low mass associated with non-radioactive species which are formed along with the radiotracer from the trace amounts of carrier found is demonstrated. Herein, we describe a pre-concentration system to detect dilute radiopharmaceutical formulations and metabolite analyses by SQ-MS. Selected examples where SQ-MS was critical for optimization of radiochemical reactions and for unequivocal characterization of radiotracers are showcased. We also illustrate examples where SQ-MS can be applied in identification of radiometal complexes and development of a new purification methodology for Pd-catalyzed radiofluorination reactions, shedding light on the identity of metal complexes present in the labelling solution.

“In-loop” [11C]CO2 fixation: Prototype and proof of concept

Carbon-11-labeled carbon dioxide is the most common feedstock for the synthesis of positron emission tomography radiotracers and can be directly used for 11C-carbonylation. Herein, we report the development of an apparatus that takes advantage of “in-loop” technologies to facilitate robust and reproducible syntheses of 11C-carbonyl-based radiotracers by [11C]CO2-fixation. Our “in-loop” [11C]CO2-fixation method is simple, efficient, and proceeds smoothly at ambient pressure and temperature. We selected model 11C-carbonyl-labeled carbamates as well as symmetrical and unsymmetrical ureas based on their widespread use in radiotracer design and our clinical research interests for proof of concept. Utility of this method is demonstrated by the synthesis of a reversible radiopharmaceutical for monoamine oxidase B, [11C]SL25.1188, and 2 novel fatty acid amide hydrolase inhibitors. These radiotracers were isolated and formulated (>3.5?GBq; 100?mCi) with radiochemical purities (>99%) and molar radioactivity (≥80?GBq/μmol; ≥2162?mCi/μmol).

Synthesis of 11C-labelled ureas by palladium(II)-mediated oxidative carbonylation

Positron emission tomography is an imaging technique with applications in clinical settings as well as in basic research for the study of biological processes. A PET tracer, a biologically active molecule where a positron-emitting radioisotope such as carbon-11 has been incorporated, is used for the studies. Development of robust methods for incorporation of the radioisotope is therefore of the utmost importance. The urea functional group is present in many biologically active compounds and is thus an attractive target for incorporation of carbon-11 in the form of [11C]carbon monoxide. Starting with amines and [11C]carbon monoxide, both symmetrical and unsymmetrical 11C-labelled ureas were synthesised via a palladium(II)-mediated oxidative carbonylation and obtained in decay-corrected radiochemical yields up to 65%. The added advantage of using [11C]carbon monoxide was shown by the molar activity obtained for an inhibitor of soluble epoxide hydrolase (247 GBq/μmol-319 GBq/μ mol). DFT calculations were found to support a reaction mechanism proceeding through an 11C-labelled isocyanate intermediate.

Synthesis of 11C-Labelled Symmetrical Ureas via the Rapid Incorporation of [11C]CO2 into Aliphatic and Aromatic Amines

An efficient method to radiolabel symmetrical [11C]ureas using 1,8-diazabicycloundec-7-ene (DBU) and cyclotron-produced [11C]CO2 has been developed. [11C]urea derivatives were obtained when aliphatic and aromatic amines were used with excellent radiochemical yields (RCYs) of over 70%. The mechanism of the reaction is proposed on the basis of control experiments. This simple and robust methodology provides a powerful tool to prepare 11C-labelled ureas previously inaccessible by existing methods and enable their utilisation for in vivo molecular imaging applications.

Palladium-mediated oxidative carbonylation reactions for the synthesis of 11C-radiolabelled ureas

Palladium(II)-mediated oxidative carbonylation reactions have been used to synthesize 11C-radiolabelled ureas via the coupling of amines with [11C]carbon monoxide, in a one-pot process. Following trapping of 11CO in a solution of copper(I) tris(3,5-dimethylpyrazolyl)borate, homocoupling reactions of primary aliphatic amines proceed in the presence of Pd(PPh3)2Cl2 to give the corresponding N,N-disubstituted [11C]ureas. Secondary amines do not produce the corresponding N,N,N,N-tetrasubsituted [11C]ureas under these conditions. This difference in reactivity allows for the formation of unsymmetrical N,N',N'-trisubstituted [11C]ureas using a mixture of a primary amine and a reactive secondary amine. The potential use of this method in positron emission tomography (PET) was demonstrated by the synthesis of the M1 muscarinic acetylcholine receptor radiotracer, [11C-carbonyl] GSK1034702.

Rapid and efficient synthesis of [11C]ureas via the incorporation of [11C]CO2 into aliphatic and aromatic amines

A rapid urea radiolabelling methodology has been developed. [ 11C]CO2 was activated by 1,8-diazabicycloundec-7-ene (DBU) in the presence of aliphatic and aromatic amines and reacted with Mitsunobu reagents to produce asymmetric 11C radiolabelled ureas in high radiochemical yields.