Bromine → Methyl 6-amino-5-bromo-2-(4-chloro-2,3-difluorophenyl)pyrimidine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

Potassium acetate (750 mg, 7.6 mmol, 3.0 equiv) and bromine (150 μL, 2.8 mmol, 1.1 equiv) were sequentially added to a stirred suspension of methyl 6-amino-2-(4-chloro-2,3-difluorophenyl)pyrimidine-4-carboxylate (760 mg, 2.5 mmol, 1.0 equiv) in glacial acetic acid (10 mL) at 23° C. The resulting thick orange mixture was stirred at 23° C. for 2 h. The reaction mixture was quenched with saturated sodium thiosulfate solution (˜50 mL) and adjusted to pH=7 using 50% sodium hydroxide solution. The resulting white mixture was diluted with water (150 mL) and extracted with dichloromethane (3×100 mL). The combined organic layers were dried (magnesium sulfate), gravity filtered, and concentrated under vacuum. The product was purified by flash chromatography (SiO2, 33% ethyl acetate in hexane) to afford the title compound as a white powder (760 mg, 79% yield): mp 175-178° C.; 1H NMR (300 MHz, CDCl3) δ 7.76 (ddd, 1H, J=9, 7, 2 Hz), 7.23 (ddd, 1H, J=9, 7, 2 Hz), 5.70 (br s, 2H), 4.01 (s, 3H); IR (neat film) 3473 (s), 3317 (s), 3179 (s), 2963 (w), 1740 (s), 1651 (s); ESIMS m/z 378 ([M+H]+).

Provenance & Evidence