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[<sup>11</sup>C]Carbon Monoxide and Aryl Triflates in Palladium-Mediated Carbonylation Reactions : Synthetic approaches to [<sup>11</sup>C]Carbonyl Compounds and [<sup>11</sup>C]Amines

<p>The usefulness of low concentrations (typically 10 to 100 <i>µ</i>M) of [<sup>11</sup>C]carbon monoxide and aryl triflates as substrates in <sup>11</sup>C-carbonylation using different nucleophiles in the presence of lithium bromide was investigated. The reactions were performed in a micro autoclave of 200 <i>µ</i>L volume and catalysed (mediated) by palladium(0). </p><p>A peripheral type benzodiazepine receptor (PBR) ligand, 1-(2-chlorophenyl)-<i>N</i>-methyl-<i>N</i>-(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 <sup>11</sup>C using this approach. The [<i>carbonyl</i>-<sup>11</sup>C]PK11195, analogues and other amides were prepared from aryl triflates and amines, and the [<i>carbonyl</i>-<sup>11</sup>C]ketones were prepared from aryl triflates and organoboranes. In the synthesis of [<i>carboxyl</i>-<sup>11</sup>C]carboxylic acids, water was utilised as nucleophile. The decay-corrected radiochemical yields were 10 to 55% for [<sup>11</sup>C]PK11195 and analogues, 2 to 63% for other [<sup>11</sup>C]amides, 10 to 75% for [<sup>11</sup>C]ketones and 25 to 65% for [<sup>11</sup>C]carboxylic acids. The specific radioactivity of the labelled compounds was in the range of 150 to 900 GBq/<i>µ</i>mol. </p><p>Some [<sup>11</sup>C]amines were prepared by a reductive amination of the corresponding<sup> </sup> [carbonyl-<sup>11</sup>C]ketones. These reactions were performed using different amines in the presence of TiCl<sub>4</sub> and NaBH<sub>3</sub>CN. The radiochemical yields of the [<sup>11</sup>C]amines varied from 2 to 78% (determined by analytical HPLC). </p><p>In order to confirm the labelling position, synthesis of selected <sup>13</sup>C-substituted compounds were performed. For each substance group/ synthesis method, a selected compound was synthesised using (<sup>13</sup>C)carbon monoxide and the <sup>13</sup>C-substituted compound was then analysed by <sup>13</sup>C NMR.</p><p>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 [<i>carbonyl</i>-<sup>11</sup>C]PK11195 and analogues.</p>

Identiferoai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-4157
Date January 2004
CreatorsRahman, Obaidur
PublisherUppsala University, Department of Chemistry, Uppsala : Acta Universitatis Upsaliensis
Source SetsDiVA Archive at Upsalla University
LanguageEnglish
Detected LanguageEnglish
TypeDoctoral thesis, comprehensive summary, text
RelationComprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, 1104-232X ; 960

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