Functionalization through Lithiation of (S)-N-(1-Phenylpropyl)-2-phenylquinoline-4-carboxamide. Application to the Labeling with Carbon-11 of NK-3 Receptor Antagonist SB 222200

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• 作者：Idriss Bennacef ; Cé ; cile Perrio ; Marie-Claire Lasne ; Louisa Barré
• 刊名：Journal of Organic Chemistry
• 出版年：2007
• 出版时间：March 16, 2007
• 年：2007
• 卷：72
• 期：6
• 页码：2161 - 2165
• 全文大小：94K
• 年卷期：v.72,no.6(March 16, 2007)
• ISSN：1520-6904

文摘

Lithiation of (S)-N-(1-phenylpropyl)-2-phenylquinoline-4-carboxamide with the complex n-BuLi/TMEDA(1/1 molar ratio) in THF at -60 C for 5 h occurred selectively at the position 3 of the quinoline ring.This selectivity was shown by the absence of racemization of the stereogenic center and the formationof the corresponding functionalized quinolines in 59-74% yield by subsequent reaction with an electrophileat -60 C for 1 h. The 3-trimethylstannyl derivative was subjected to a Stille reaction using methyl,phenyl, or thienyliodide to afford the alkyl or aryl quinolines in moderate to good yields. This methodologywas successfully applied to the radiosynthesis of [¹¹C]SB 222200 using methyl iodide labeled with carbon-11 (⁺ emitter, t_1/2 = 20.4 min) for the in vivo study of NK-3 receptor by positron emission tomography(48-58% radiochemical yields from [¹¹C]CH₃I, decay corrected, 45 min total synthesis time).