Observation of differential reactivity of cyclic amines in S_N2 and S_NAr displacement reactions in the course of synthesizing C-6, C-7 substituted quinolinecarbonitrile MEK1 kinas

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• 作者：Darrin W. Hopper ; Minu Dutia ; Dan M. Berger ; Dennis W. Powell
• 关键词：Alkenylation ; Alkylation ; Desulfurization ; Sultams
• 刊名：Tetrahedron Letters
• 出版年：2008
• 出版时间：1 January 2008
• 年：2008
• 卷：49
• 期：1
• 页码：137-140
• 全文大小：110 K

文摘

We have previously reported on a series of 4-anilino-6,7-dialkoxy-3-quinolinecarbonitriles as potent inhibitors of MEK1 kinase. Herein, we describe our synthetic efforts toward a series of 4-anilino-6-alkoxy-7-amino-3-quinolinecarbonitriles. In the course of this work, we were able to rapidly construct a library of 4-anilino-6-alkoxy-7-amino-3-quinolinecarbonitriles by simultaneous or sequential S_N2 (displacement) reactions on the C-6 chloroalkoxy moiety and S_NAr (addition/elimination) reactions at C-7 with nucleophilic amines.