3964-04-3

Light yellow solid

4-Bromoquinoline is used to prepare bone morphogenetic protein (BMP) signaling inhibitors. It is also used to synthesize novel azalides derived from 16-membered macrolides.

The Journal of Organic Chemistry, 72, p. 2232, 2007 DOI: 10.1021/jo062168u

Step 1: Phosphorus tribromide (7.61 g, 28.2 mmol) was slowly added dropwise to a stirred solution of anhydrous N,N-dimethylformamide (DMF, 30 mL) of 4-hydroxyquinoline (4.00 g, 27.6 mmol) for 10 min under nitrogen protection. The reaction mixture formed a red suspension and continued to stir under nitrogen atmosphere for 30 min. The reaction was monitored by thin layer chromatography (TLC) and after confirming the complete consumption of the raw material, the reaction mixture was quenched in an ice bath and stirred for 30 minutes. Subsequently, the pH of the reaction mixture was adjusted with saturated sodium bicarbonate solution (20 mL) to about 10. The reaction mixture was extracted with ethyl acetate (2 x 100 mL), the organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography eluting with a gradient of dichloromethane/methanol (0% to 10%) to give 4-bromoquinoline (5.04 g, 88% yield) as a yellow solid. The product was detected by liquid chromatography-mass spectrometry (LCMS, ESI) and showed [M+H]+ peak of 208; 1H NMR (400 MHz, chloroform-d) δ ppm: 8.69 (d, J = 4.69 Hz, 1H), 8.20 (ddd, J = 8.39, 0.88 Hz, 1H), 8.08-8.16 (m, 1H), 7.78 ( ddd, J = 8.39, 6.98, 1.37 Hz, 1H), 7.71 (d, J = 4.69 Hz, 1H), 7.66 (ddd, J = 8.31, 7.04, 1.15 Hz, 1H).

[1] Journal of the American Chemical Society, 2012, vol. 134, # 12, p. 5652 - 5661
[2] Journal of Organic Chemistry, 2007, vol. 72, # 6, p. 2232 - 2235
[3] Patent: WO2014/121883, 2014, A1. Location in patent: Page/Page column 51
[4] Angewandte Chemie - International Edition, 2012, vol. 51, # 37, p. 9311 - 9316
[5] Angew. Chem., 2012, vol. 124, # 37, p. 9445 - 9450,6