A convenient approach is described for the general synthesis of 4-aminoquinoline-3-carbonitrile scaffolds. A series of substituted anthranilonitriles bearing electron-donating and-withdrawing groups on the arene react with 3-bromopropanenitrile and t-BuOK in anhydrous DMF at ca. 24 °C. A wide variety of bases have been used to optimize selective mono-N-alkylation. The best conditions lead to the corresponding 2-(cyanoethylamino)benzonitriles in moderate or good yields. Thorpe–Ziegler cyclization of the N-unprotected 2-(cyanoethylamino)benzonitrile analogs with t-BuLi in THF at -78 °C gives 4-amino, 4-amino-6-methyl, 4-amino-7-methyl, and 4-amino-6-fluoro-quinoline-3-carbonitriles in moderate yields. Owing to their vicinal amino and cyano functional groups that can function as enaminonitrile moieties, 4-aminoquinoline-3-carbonitriles are attractive building blocks frequently used in ring construction.


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一种简便的4-氨基喹啉-3-甲腈及其衍生物的合成新方法

描述了一种方便的方法，用于 4-氨基喹啉-3-腈支架的一般合成。一系列在芳烃上带有给电子和吸电子基团的取代邻氨基苯腈与 3-溴丙腈和t - BuOK 在无水 DMF 中反应，时间约为 24℃。多种碱已用于优化选择性单-N-烷基化。最佳条件以中等或良好的产率产生相应的 2-(氰基乙基氨基)苄腈。N-未保护的 2-(氰基乙基氨基)苄腈类似物与t的索普-齐格勒环化-BuLi 在 THF 中 -78 °C 以中等收率生成 4-氨基、4-氨基-6-甲基、4-氨基-7-甲基和 4-氨基-6-氟代喹啉-3-腈。由于它们的邻氨基和氰基官能团可以作为烯氨基腈部分，4-氨基喹啉-3-腈是环结构中常用的有吸引力的结构单元。