[Synthesis]
The general procedure for the synthesis of 4-amino-2-chloroquinoline from 2,4-dichloroquinoline is as follows: the synthesis of compound 9 has been reported in the literature [von Btichi, J. et al. Die Tuberkulostatische Wirkung von 2-Oxy-4-amino-chinolin Derivaten. Helv. Chim. Acta. 1949, 32, 1806-1814; Wojahn, H. Untersuchungen ber den Zusammenhang von chemischer Konstitution und anasthesierender Wirkung bei 2- Alkoxy-chinolin Derivaten. Arch. Pharm. 1936, 274, 83-106]. However, in the present experiments, compound 9 was prepared by the following method. the brief procedure was as follows: compound 8 (0.35 g, 1.8 mmol) was suspended in 28-30% aqueous ammonia solution (3 mL). The reaction was carried out in a microwave reactor at 160 °C for 2.5 hours. Upon completion of the reaction, the ammonia was removed by evaporation. The product was purified by column chromatography using dichloromethane solution containing 3% methanol as eluent. Yield: 0.14 g (44%).1H NMR (CDCl3) δ 4.83 (broad single peak, 2H, NH2), 6.62 (single peak, 1H, aromatics), 7.43-7.51 (multiple peaks, 1H, aromatics), 7.63-7.73 (multiple peaks, 2H, aromatics), 7.89-7.95 (multiple peaks, 1H, aromatics).13C NMR ( 600 MHz, CDCl3) δ 103.07, 117.60, 120.08, 125.27, 129.13, 130.46, 148.26, 151.40, 151.41. |
[References]
[1] Journal of Medicinal Chemistry, 2009, vol. 52, # 4, p. 926 - 931
[2] Patent: WO2010/20981, 2010, A1. Location in patent: Page/Page column 30; 2/2
[3] Journal of Photochemistry and Photobiology A: Chemistry, 2017, vol. 332, p. 72 - 86 |