S. Kitson, Stuart Jones, W. Watters
Mar 1, 2010
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Influential Citations
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Journal
Journal of Labelled Compounds and Radiopharmaceuticals
Abstract
A method has been developed for the carbon-14 radiosynthesis of [14C]XEN-D0401, a 4-(2-hydroxyphenyl)quinolin-2(1H)-one derivative. The radiosynthetic route involves a series of ortho-lithiations directed by both 2-methoxymethyl (MOM) and pivaloyl protecting groups. This is demonstrated in the first key radiochemical step between the reaction of 5-chloro-2-methoxymethoxy-[carboxyl-14C]benzoic acid methyl ester [14C]-3 and the ortho-lithiated intermediate generated from 2,2-dimethyl-N-(4-trifluoromethylphenyl)-propionamide (2) to afford the protected benzophenone [14C]-4. The other key radiochemical step utilizes a variation of the Friedlander quinoline synthesis, which involves a base catalysed, one-pot condensation process between (2-amino-5-trifluoromethyl-phenyl)-(5-chloro-2-methoxymethoxy-phenyl)-[14C]methanone [14C]-5 and γ-butyrolactone to give MOM-protected [14C]-6. On MOM deprotection, [14C]XEN-D0401 was isolated with a radiochemical purity of >97%, with a specific activity of 55 mCi/mmol from seven radiochemical steps, starting from barium [14C]carbonate in a radiochemical yield of 10.5%. Copyright © 2010 John Wiley & Sons, Ltd.