Application
2-Chloro-1,8-Naphthidine has shown great activity in the design of novel antibiotics and drugs for the treatment of cardiovascular diseases, and is an important breakthrough for future drug development.
Synthesis
General procedure for the synthesis of 2-chloro-1,8-naphthyridine from 1,8-naphthyridin-2(1H)-one: Phosphoryl chloride (86 mL, 924 mmol) was added to 1,8-naphthyridin-2(1H)-one (9.00 g, 61.6 mmol), and the reaction mixture was heated to 100°C and maintained for 1 hour. Upon completion of the reaction, the mixture was cooled and the excess phosphorus trichloride was removed by evaporation. The residue was dissolved in dichloromethane (100 mL) and alkalized by slowly adding saturated sodium bicarbonate solution. The organic layer was separated, dried with anhydrous sodium sulfate, filtered and the solvent evaporated to afford the target compound 2-chloro-1,8-naphthyridine as a white solid (7 g, 70% yield). The product was characterized by 1H NMR (400 MHz, CDCl3): δ 7.50 (1H, d, J=8.4 Hz), 7.52 (1H, dd, J=8.1 Hz and 4.3 Hz), 8.16 (1H, d, J=8.4 Hz), 8.22 (1H, dd, J=8.1 Hz and 2.0 Hz), 9.12 (1H, dd, J= 4.3 Hz and 2.0 Hz).
References
[1] Journal of the American Chemical Society, 2015, vol. 137, # 8, p. 2996 - 3003
[2] Patent: WO2005/47279, 2005, A1. Location in patent: Page/Page column 50
[3] Patent: WO2016/130968, 2016, A1. Location in patent: Page/Page column 161
