Synthesis
General procedure for the synthesis of 4-chloro-6-bromocinnoline from 6-bromocinnolin-4-ol: Thionyl chloride (3 mL) and N,N-dimethylformamide (30 μL) were sequentially added to 6-bromoquinolin-4(1H)-one (300 mg, 1.33 mmol), and the reaction mixture was heated to reflux for 30 min. After completion of the reaction, the reaction solution was concentrated under reduced pressure and saturated aqueous sodium bicarbonate was added to the residue and extracted with ethyl acetate. The organic layers were combined, washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and distilled under reduced pressure to remove the solvent. The resulting crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate) to afford 4-chloro-6-bromocinnoline (288 mg, 89% yield) as a yellow solid.
References
[1] Patent: JP6378918, 2018, B2. Location in patent: Paragraph 0721; 0724
[2] Patent: US2015/259331, 2015, A1. Location in patent: Paragraph 0192
[3] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 20, p. 6832 - 6846
[4] Patent: US2003/187026, 2003, A1
[5] Journal of the Chemical Society, 1950, p. 384,389
