[Synthesis]
The general procedure for the synthesis of 2-hydroxy-3-methyl-5-bromopyrazine from 2-hydroxy-3-methylpyrazine was as follows: to a solution of 3-methylpyrazin-2-ol (1.5 g, 13.62 mmol) in anhydrous N,N-dimethylformamide (DMF, 20 mL) was added batchwise at 0 °C N-bromosuccinimide (NBS, 2.67 g, 14.98 mmol). The reaction mixture was slowly warmed to room temperature and stirred overnight. Upon completion of the reaction, the mixture was poured into ice water and extracted with a solvent mixture of isopropanol (IPA)/dichloromethane (DCM, 1/5, v/v). The organic phases were combined, dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with 80% ethyl acetate/hexane (v/v) as eluent to afford 2-hydroxy-3-methyl-5-bromopyrazine as white solid (1.97 g, 10.42 mmol, 77% yield). The product was analyzed by mass spectrometry (LCMS) with measured m/z = 189.0 [M+H]+ (calculated exact mass of C5H5BrN2O: 188.0).1H NMR (400 MHz, DMSO-d6) δppm: 2.27 (d, J = 0.5 Hz, 3H), 7.73 (s, 1H), 12.3 (s, 1H). |