Synthesis Example 1 Preparation of 2-amino-3,5-dibromo-6-chloropyrazine (4): To a solution of 2-amino-6-chloropyrazine (3) (8.00 g, 61.8 mmol) in acetonitrile (80 mL) was slowly added N-bromosuccinimide (NBS) (27.5 g, 155 mmol) at 0 °C. After addition, the reaction mixture was gradually warmed to room temperature and stirred overnight (18 hours). After completion of the reaction, water was added to the mixture and the product was extracted with ether (3 x 80 mL). The organic phases were combined and washed sequentially with water (1 x 80 mL) and saturated saline (1 x 80 mL), then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate= 3/1, v/v) to afford 2-amino-3,5-dibromo-6-chloropyrazine (4) (16.8 g, 58.5 mmol, 94.7% yield) as a yellow solid. tlc Rf = 0.31 (Expander: n-hexane/ethyl acetate= 4/1, v /v); 1H NMR (500MHz, CDCl3) δ 5.14 (s, 2H); 13C NMR (126MHz, CDCl3) δ 120.7, 122.0, 146.1, 151.0.
