[Synthesis]
3,3-Diethoxypropionitrile (1.80 mL, 12.00 mmol), 2-amino-4-bromobenzaldehyde (2 g, 10.00 mmol) and p-toluenesulfonic acid monohydrate (0.380 g, 2.000 mmol) were mixed in toluene (30 mL). The reaction mixture was heated under reflux conditions for 3 hours by a Dean-Stark apparatus. After completion of the reaction, it was cooled to room temperature and the solvent was removed by evaporation under reduced pressure. The residue was dissolved in a small amount of DMF, diluted with chloroform and washed sequentially with water and sodium bicarbonate solution. The aqueous layer was extracted with chloroform, the organic phases were combined, washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by fast column chromatography (eluent: dichloromethane/methanol, 0-3%) and the resulting product was ground in ether to give 7-bromo-3-cyanoquinoline (1.75 g, 75% yield).1H NMR (400 MHz, DMSO-d6) δ ppm: 7.95 (dd, J = 8.72, 1.89 Hz, 1H), 8.08 (d, J = 8.84 Hz, 1H), 8.38 (d, J = 2.02 Hz, 1H), 9.13 (d, J = 1.52 Hz, 1H), 9.21 (d, 1H). |
[References]
[1] Patent: WO2013/28447, 2013, A1. Location in patent: Page/Page column 119-120
[2] Patent: WO2013/52716, 2013, A1. Location in patent: Page/Page column 50; 65
[3] Patent: WO2013/177253, 2013, A2. Location in patent: Page/Page column 61
[4] Patent: WO2014/8223, 2014, A2. Location in patent: Page/Page column 73 |