4-Amino-2-bromoquinoline

Synthesis

The general procedure for the synthesis of 2-bromoquinolin-4-amines from 2-bromo-3-nitroquinolines is as follows: compound 5 was prepared by reference to literature methods [Kornblum, N. et al. Reduction of optically active 2-nitrooctane and α-phenylnitroethane. J. Am. Chem. Soc. 1955, 77, 6266-6269; Den Hertog, H. J.; Buurman, D. J. Rec. Trav. Chim. Pays-Bas 1972, 91, 841-849]. The procedure was as follows: compound 4 (1.82 g, 7.2 mmol) was dissolved in acetic acid, iron powder (5 eq.) was added, and the reaction mixture was stirred at 65 °C for 2.5 hours. After completion of the reaction, the iron powder was removed by filtration and washed with dichloromethane (DCM). Subsequently, the pH was adjusted to 9 with 2 M sodium hydroxide solution, filtered again and the residue was washed with ammonia. The aqueous layer was extracted with dichloromethane and the organic phase was dried with anhydrous magnesium sulfate and concentrated under reduced pressure. The product was purified by column chromatography using dichloromethane as eluent. The target product was obtained as 0.69 g in 43% yield. The structure of the product was confirmed by 1H NMR (CDCl3) and 13C NMR (CDCl3): 1H NMR (CDCl3) δ 4.81 (broad peak, 2H, NH2), 6.76 (single peak, 1H, Ar), 7.48 (triple peak, 1H, J = 7.3 Hz, Ar), 7.62-7.73 (multiple peaks, 2H, Ar), 7.94 (double peaks) , 1H, J = 8.76 Hz, Ar); 13C NMR (CDCl3) δ 106.65, 117.82, 120.21, 125.37, 129.19, 130.45, 148.78, 150.90.

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 29; 1/2