[Synthesis]
General procedure for the synthesis of 8-chloro-1,7-naphthyridine from 1,7-naphthyridin-8(7H)-one: 1,7-naphthyridin-8(7H)-one (2.0 g, 13.7 mmol) was dissolved in phosphorus triclopyr (20 mL) and heated and refluxed at 100 °C for 16 h. The progress of the reaction was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure to remove the solvent. The residue was neutralized by adding saturated sodium bicarbonate solution (20 mL) and subsequently extracted with ethyl acetate (3 x 25 mL). The organic phases were combined, washed with saturated saline (25 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the resulting crude product was purified by silica gel column chromatography to afford 8-chloro-1,7-naphthyridine (1.4 g, 62% yield) using dichloromethane/methanol (98:2 to 95:5, v/v) as eluent. Mass spectrum (EI) m/z: 165.3 ([M+H]+); 1H NMR (400 MHz, DMSO-d6) δ: 7.64 (d, J = 6.0 Hz, 1H), 7.70 (dd, J = 4.0, 8.4 Hz, 1H), 8.22 (dd, J = 1.6, 8.4 Hz, 1H), 8.40 (d, J = 6.0 Hz. 1H), 9.15 (dd, J = 1.6, 4.0 Hz, 1H). |