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[11C]Carbon Monoxide and Aryl Triflates in Palladium-Mediated Carbonylation Reactions: Synthetic approaches to [11C]Carbonyl Compounds and [11C]Amines
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The usefulness of low concentrations (typically 10 to 100 µM) of [11C]carbon monoxide and aryl triflates as substrates in 11C-carbonylation using different nucleophiles in the presence of lithium bromide was investigated. The reactions were performed in a micro autoclave of 200 µL volume and catalysed (mediated) by palladium(0).

A peripheral type benzodiazepine receptor (PBR) ligand, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-carboxamide (PK11195) and its structural analogues including an irreversible ligand for PBR, some other amides, ketones and carboxylic acids, were all labelled with 11C using this approach. The [carbonyl-11C]PK11195, analogues and other amides were prepared from aryl triflates and amines, and the [carbonyl-11C]ketones were prepared from aryl triflates and organoboranes. In the synthesis of [carboxyl-11C]carboxylic acids, water was utilised as nucleophile. The decay-corrected radiochemical yields were 10 to 55% for [11C]PK11195 and analogues, 2 to 63% for other [11C]amides, 10 to 75% for [11C]ketones and 25 to 65% for [11C]carboxylic acids. The specific radioactivity of the labelled compounds was in the range of 150 to 900 GBq/µmol.

Some [11C]amines were prepared by a reductive amination of the corresponding [carbonyl-11C]ketones. These reactions were performed using different amines in the presence of TiCl4 and NaBH3CN. The radiochemical yields of the [11C]amines varied from 2 to 78% (determined by analytical HPLC).

In order to confirm the labelling position, synthesis of selected 13C-substituted compounds were performed. For each substance group/ synthesis method, a selected compound was synthesised using (13C)carbon monoxide and the 13C-substituted compound was then analysed by 13C NMR.

A synthetic route was developed for the preparation of 1-(2-chloro-phenyl)-isoquinolin-3-yl trifluoromethanesulfonate used as the precursor in the synthesis of [carbonyl-11C]PK11195 and analogues.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2004. , p. 40
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 960
Keywords [en]
Organic chemistry, [11C]Carbon monoxide, Aryl triflates, Carbonylation
Keywords [sv]
Organisk kemi
National Category
Organic Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-4157ISBN: 91-554-5930-7 (print)OAI: oai:DiVA.org:uu-4157DiVA, id: diva2:164368
Public defence
2004-05-07, B41, BMC, Uppsala, 10:15
Opponent
Supervisors
Available from: 2004-04-13 Created: 2004-04-13Bibliographically approved
List of papers
1. Syntheis of 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-[11C]carboxamide ([11C-carbonyl]PK11195 and some analogues using [11C]carbon monoxide and 1-(2-chlorophenyl)isoquinolin-3-yl triflate
Open this publication in new window or tab >>Syntheis of 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-[11C]carboxamide ([11C-carbonyl]PK11195 and some analogues using [11C]carbon monoxide and 1-(2-chlorophenyl)isoquinolin-3-yl triflate
2002 In: Journal of the Chemical Society, Perkin Trans. 1, p. 2699-2703Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-91581 (URN)
Available from: 2004-04-13 Created: 2004-04-13Bibliographically approved
2. Aryl Triflates and [11C]/(13C)Carbon Monoxide in the Synthesis of 11C-/13C-Amides
Open this publication in new window or tab >>Aryl Triflates and [11C]/(13C)Carbon Monoxide in the Synthesis of 11C-/13C-Amides
2003 In: Journal of Organic Chemistry, Vol. 68, no 9, p. 3558-3562Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-91582 (URN)
Available from: 2004-04-13 Created: 2004-04-13Bibliographically approved
3. Synthesis of 11C-/13C-Ketones by Suzuki Coupling
Open this publication in new window or tab >>Synthesis of 11C-/13C-Ketones by Suzuki Coupling
2004 In: European Journal of Organic Chemistry, p. 474-478Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-91583 (URN)
Available from: 2004-04-13 Created: 2004-04-13Bibliographically approved
4. Organic Bases as Additives to Improve the Radiochemical Yields of [11C]Ketones Prepared by the Suzuki Coupling Reaction
Open this publication in new window or tab >>Organic Bases as Additives to Improve the Radiochemical Yields of [11C]Ketones Prepared by the Suzuki Coupling Reaction
2004 (English)In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, Vol. 2004, no 12, p. 2674-2678Article in journal (Refereed) Published
Abstract [en]

The Suzuki cross-coupling reaction was employed in the syntheses of eight new [11C-carbonyl]ketones. The reactions between the corresponding boronic acids and the corresponding triflates were performed in the presence of [11C]carbon monoxide and a palladium(0) complex as the catalyst. Lithium bromide was added to facilitate the reactions, and different bases were tested to improve the radiochemical yields. All the ketones were synthesised, with the achievement of isolated radiochemical yields (decay-corrected) of between 14 and 74%. Important improvements in the radiochemical yield were achieved by use of tetrabutylammonium fluoride in the synthesis of ketones incorporating alkyl groups, while potassium tert-butoxide was the best base among those tested for improving the radiochemical yields in the syntheses of biaryl ketones. The optimal amount of base was determined in all cases. Only for compounds 3e and 3h were better radiochemical yields obtained when no base was used. No radiochemical impurities were detected after isolation of the compounds. The specific radioactivity for compound 3a was determined, and a value of 200 GBq/μmol was obtained. Compound 3b was labelled simultaneously with [11C] and (13C)carbon monoxide and the position of the labelled atom was determined and confirmed by 13C NMR spectrometry. Tetrabutylammonium fluoride and potassium tert-butoxide are reported as useful bases for Suzuki carbonylation with [11C]/(13C)carbon monoxide.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-91584 (URN)10.1002/ejoc.200400038 (DOI)
Available from: 2004-04-13 Created: 2004-04-13 Last updated: 2017-12-14Bibliographically approved
5. Synthesis of [11C]/(13C)Amines via Carbonylation followed by Reductive Amination
Open this publication in new window or tab >>Synthesis of [11C]/(13C)Amines via Carbonylation followed by Reductive Amination
In: Organic & Biomolecular ChemistryArticle in journal (Refereed) Submitted
Identifiers
urn:nbn:se:uu:diva-91585 (URN)
Available from: 2004-04-13 Created: 2004-04-13Bibliographically approved
6. Synthesis of Aryl [11C]/(13C)Carboxylic Acids using Aryl Triflates and [11C]/(13)Carbon Monoxide
Open this publication in new window or tab >>Synthesis of Aryl [11C]/(13C)Carboxylic Acids using Aryl Triflates and [11C]/(13)Carbon Monoxide
Manuscript (Other academic)
Identifiers
urn:nbn:se:uu:diva-91586 (URN)
Available from: 2004-04-13 Created: 2004-04-13 Last updated: 2010-01-13Bibliographically approved
7. 11C-Labelling of 1-(2-chlorophenyl)-N-(1-methylpropyl)-N-(2-isothiocyanatoethyl)isoquinoline-3-carboxamide
Open this publication in new window or tab >>11C-Labelling of 1-(2-chlorophenyl)-N-(1-methylpropyl)-N-(2-isothiocyanatoethyl)isoquinoline-3-carboxamide
Manuscript (Other academic)
Identifiers
urn:nbn:se:uu:diva-91587 (URN)
Available from: 2004-04-13 Created: 2004-04-13 Last updated: 2010-01-13Bibliographically approved

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