General procedure for the synthesis of 5-bromo-3-chloropyrazin-2-one from 5-bromo-3-chloropyrazin-2-amine: 5-bromo-3-chloropyrazin-2-amine (9.00 g, 43.2 mmol) was dissolved in concentrated sulfuric acid (35 mL) at 0 °C and added slowly and dropwise to a pre-prepared sodium nitrite (3.52 g, 51.0 mmol) concentrated sulfuric acid (20 mL ) solution. The reaction mixture was heated at 40°C for 1 hr, then cooled to room temperature and slowly poured into crushed ice (400 mL) to quench the reaction. The reaction mixture was extracted with ethyl acetate (200 mL), the organic phase was dried over anhydrous sodium sulfate and filtered, and concentrated under reduced pressure to afford the target product 5-bromo-3-chloropyrazin-2(1H)-one (6.13 g, 68% yield) as a brown solid. The product characterization data were as follows: melting point 175-177 °C; IR spectra (νmax/cm-1) 3019 (Ar-H), 1653 (C=O); NMR hydrogen spectrum (500 MHz, CD3OD) δH 7.72 (1H, s, 6-H); NMR carbon spectra (125 MHz, CDCl3) δC 114.2, 127.6, 146.4, 154.0; liquid chromatography-mass spectrometry (LC-MS, 6 min) m/z 213, 211, 209 ([M+H]+); high-performance liquid chromatography (HPLC) retention time (tR) 2.54 min, purity >99%; high-resolution mass spectrometry (HRMS) measured values: [M+H]+ m/z 208.9113, calculated value 208.9112.
