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 kinase inhibitors

摘要

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.