Synthesis
GENERAL STEPS: A mixture of 4-bromo-2,6-dimethylaniline (1.90 g, 9.50 mmol) and cuprous(I) cyanide (1.71 g, 19.1 mmol) in N-methylpyrrolidone (NMP, 25 mL) was reacted with stirring at 160 °C overnight. Upon completion of the reaction, the mixture was cooled to room temperature. Subsequently, water (10 mL) and ammonium hydroxide solution (10 mL) were added to the reaction mixture and extracted with ethyl acetate (3 × 50 mL) to separate the products. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by fast column chromatography (dichloromethane as eluent) to afford 4-amino-3,5-dimethylbenzonitrile 1.19 g (86% yield, 1.39 g theoretical yield). The product was analyzed by LCMS (Method B) with a retention time (RT) of 1.925 min and a molecular ion peak (MH+) of 147. 1H NMR (500 MHz, CDCl3) δ 7.22 (s, 2H), 2.18 (s, 6H).
References
[1] Patent: US2006/287287, 2006, A1. Location in patent: Page/Page column 34
[2] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 9, p. 3115 - 3126
[3] Journal of Heterocyclic Chemistry, 1997, vol. 34, # 1, p. 269 - 272
[4] Patent: US2008/146595, 2008, A1. Location in patent: Page/Page column 29; 30
[5] Patent: WO2006/79656, 2006, A1. Location in patent: Page/Page column 20
