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

Abdul Karim Haji Dheere; Salvatore Bongarzone; Carlotta Taddei; Ran Yan; Antony D. Gee

doi:10.1055/s-0034-1381055

Synlett, Inhaltsverzeichnis

Synlett 2015; 26(16): 2257-2260
DOI: 10.1055/s-0034-1381055

letter

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

Abdul Karim Haji Dheere

Division of Imaging Sciences and Biomedical Engineering, King’s College London, 4th Floor Lambeth Wing, London, SE1 7EH, UK eMail: antony.gee@kcl.ac.uk

,

Salvatore Bongarzone

Division of Imaging Sciences and Biomedical Engineering, King’s College London, 4th Floor Lambeth Wing, London, SE1 7EH, UK eMail: antony.gee@kcl.ac.uk

,

Carlotta Taddei

Division of Imaging Sciences and Biomedical Engineering, King’s College London, 4th Floor Lambeth Wing, London, SE1 7EH, UK eMail: antony.gee@kcl.ac.uk

,

Ran Yan

Division of Imaging Sciences and Biomedical Engineering, King’s College London, 4th Floor Lambeth Wing, London, SE1 7EH, UK eMail: antony.gee@kcl.ac.uk

,

Antony D. Gee*

Division of Imaging Sciences and Biomedical Engineering, King’s College London, 4th Floor Lambeth Wing, London, SE1 7EH, UK eMail: antony.gee@kcl.ac.uk

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Abstract

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Abstract

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.

Key words

carbon-11 - carbon dioxide - Mitsunobu reaction - symmetrical urea - DBU

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Referenzen

References and Notes

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6 See Supporting Information for full experimental details and compound characterization. Synthesis of Compound 1: Diisopropylethylamine (194 mg, 1.50 mmol) was added to mixture of 1-methylpiperazine (50 mg, 0.50 mmol), and 4-methylpiperazin-l-ylcarbonyl chloride (122 mg, 0.75 mmol) in CH₂Cl₂ (20 mL). The resulting mixture was stirred at r.t. for 1 h. Then, the mixture was concentrated and recrystallised from EtOH to give 1 (30 mg, 27%). ¹H NMR (400 MHz, CDCl₃): δ = 3.59 (m, 8 H), 2.56 (m, 8 H), 2.90 (s, 6 H). ¹³C NMR (100 MHz, CD₃OD): δ = 163.65, 54.03, 45.04, 43.79. HRMS: m/z [M + H]⁺ calcd for C₁₁H₂₂N₄O: 227.1794; found: 227.2003.
7 General Radiolabelling Procedure of [¹¹C]Ureas: [¹¹C]CO₂ from the cyclotron target was bubbled in a stream of helium gas at a flow rate of 1.4 mL/min post target depressurisation directly into a reaction vial containing an amine (18.3 μmol) and DBU (0.13 μL, 0.9 μmol) in MeCN (300 μL). The resulting solution was stirred and heated at 50 °C for 1 min. In a separate vial, PBu₃ (9 μL, 36.6 μmol) was added to a solution containing DBAD (8 mg, 36.6 μmol) in MeCN (100 μL) under argon at r.t. The resulting solution was transferred into the reaction mixture and stirred for 4 min at 50 °C. The reaction was quenched with H₂O and the crude product was analysed by radio-HPLC

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Zusatzmaterial

Supporting Information