General procedure for the synthesis of 8-bromo-1,7-naphthyridin-6-amine from 3-(cyanomethyl)-2-cyanopyridine: (3) Synthesis of 8-bromo-1,7-naphthyridin-6-amine. In a 50 mL round-bottomed flask, hydrobromic acid (317 μL, 5868 μmol) and 30% acetic acid were added. Subsequently, a solution of 3-(cyanomethyl)-2-cyanopyridine (280 mg, 1956 μmol) dissolved in acetic acid (0.5 mL) was added slowly dropwise at 0 °C. The reaction mixture was stirred continuously at 0 °C for 30 min. Upon completion of the reaction, the solid product was collected by filtration and washed with 50% ethyl acetate/hexane mixture. The resulting solid was treated with saturated sodium bicarbonate solution. Next, the pH was adjusted with sodium bicarbonate solution (5 mL) followed by extraction with ethyl acetate (2 x 50 mL). The organic phases were combined, washed with saturated sodium chloride solution (5 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with 40% ethyl acetate/hexane as eluent to give 8-bromo-1,7-naphthyridin-6-amine (312 mg, 71% yield). Mass spectrum (ESI positive ion mode) m/z: calculated values C8H6BrN3 [M+H]+ 223.0, 225.0; measured values 224.0, 226.0. 1H NMR (300 MHz, chloroform-d) δ ppm: 4.63 (s, 2H), 6.61 (s, 1H), 7.42 (dd, J = 8.48, 4.09 Hz, 1H) , 7.85 (dd, J = 8.48, 1.61 Hz, 1H), 8.78 (dd, J = 3.95, 1.61 Hz, 1H).
