318276-72-1

Synthesis of Example 34F 6-Bromocinnoline: Example 34E (3.5 g, 14 mmol) was dissolved in water (50 mL) and heated to reflux. Subsequently, a solution of CuSO4 (2.8 g, 17.5 mmol) in water (20 mL) was added slowly dropwise to the reaction system and kept at reflux for 2 hours. After completion of the reaction, the reaction was cooled to room temperature and the pH was adjusted with saturated aqueous NaHCO3 solution to 7. The reaction mixture was extracted with ethyl acetate (2 x 25 mL), the organic phases were combined and concentrated. The crude product was purified by fast column chromatography on silica gel with the eluent being a 1:1 hexane/ethyl acetate solvent mixture to give the final target product 6-bromocinnoline (0.7 g, 24% yield).

[1] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 20, p. 6832 - 6846
[2] Patent: US2003/187026, 2003, A1
[3] Patent: US2003/199511, 2003, A1. Location in patent: Page/Page column 27
[4] Journal of the Chemical Society, 1950, p. 392,395