Scott B. Tran, B. Maxwell, Shiang-yuan Chen
May 30, 2009
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0
Influential Citations
10
Citations
Journal
Journal of Labelled Compounds and Radiopharmaceuticals
Abstract
Radiolabelled drug lead candidate leukocyte function-associated antigen 1 antagonist [ 14 C]spyrocyclic hydantoin: 5-(((5S,9R)-9-(4-[ 14 C]-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl)methyl)thiophene-3-carboxylic acid, 12, was conveniently prepared in three radiochemical steps from (5S,9R)-tert-butyl 9-(4-bromophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonane-7-carboxylate 9. The radiochemical yield of 12 was 28.5% from the resolved bromide 9. The preparation of the racemic spyrocyclic hydantoin 3 was obtained via a [3+2]dipolar cycloaddition reaction between 2 and N-benzyl-N-(methoxymethyl)trimethylsilylmethylamine. The introduction of [ 14 C] cyanide was completed via a palladium (0) catalyzed reaction by the addition of Zn( 4 CN) 2 to aryl bromide 9. The radiochemical and chiral purities of 12 determined by high-performance liquid chromatography were 98.7 and 99.7%, respectively. The specific activity of 12 was 87.5 μCi/mg (48.6 mCi/mmol).