Synthesis of 2-(4-((6-bromo-3-nitroquinolin-4-yl)amino) phenyl)-2-methylpropanenitrile

bromo-3-nitroquinolin-4-yl)amino)phenyl)-2-methylpropanenitril(7) is an important intermediate in many PI3K/mTOR inhibitors. The compound 5 was synthesized from 6-bromoquinolin-4-ol (1) and 2-(4-nitrophenyl)acetonitrile(4) through five steps including nitration, chlorination, alkylation, reduction and substitution. These structures were confirmed by 1 HNMR and MS spectrum. The synthetic method of 7 was optimized and can be used to synthesize the derivatives of NVP-BEZ235. 2- (4- (( 6-bromo-3-nitroquinolin-4-yl)amino) phenyl) -2-methylpropanenitrile is a key intermediate for the synthesis of quinoline inhibitors. Compound 7 was synthesized from 6-bromo-4-chloro-3-nitroquinoline(3) and 2-(4-aminophenyl)-2 -methylpropanenitrile(6)(Fig.2). In this paper, we summarized and optimized the synthetic methods of compound 1.