Synthesis
General procedure for the synthesis of 2-amino-5-bromo-6-methylpyrazine from 2-amino-6-methylpyrazine: 6-amino-2-methylpyrazine (100 mg, 1.0 eq.) was dissolved in a solvent mixture of DMSO (4.6 mL) and water (0.2 mL) under an inert atmosphere and cooled in an ice bath. To this solution was added N-bromosuccinimide (NBS, 179 mg, 1.1 eq.) in three portions. The reaction mixture was light yellow in color and stirred for 15 minutes, then the ice bath was removed and stirring was continued for 5 hours at room temperature. After completion of the reaction, the reaction was quenched with saturated NaHCO3 solution (25 mL) and extracted with ethyl acetate (EtOAc, 30 mL). The organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by fast column chromatography afforded the target compound 2-amino-5-bromo-6-methylpyrazine (Compound 10) as a light yellow solid in 36% yield.1H-NMR (400 MHz, DMSO-d6): δ 2.34 (s, 3H, CH3), 6.52 (s, 2H, NH2), 7.49 (s, 1H, Ar-H). Mass spectrum (ESI): m/z 188.2 ([M+H]+, 79Br).
References
[1] Patent: EP2666775, 2013, A1. Location in patent: Paragraph 02222
[2] Patent: WO2013/174822, 2013, A1. Location in patent: Page/Page column 86
