General procedure for the synthesis of 3,5-dibromo-2-chloropyrazine from 2-amino-3,5-dibromopyrazine: titanium(IV) chloride (174 g, 926 mmol) was added to a solution of 2-amino-3,5-dibromopyrazine (234 g, 932 mmol) in dichloromethane (DCM, 700 mL), followed by slow addition of tert-butyl nitrite (572 g, 5.55 mol). The reaction mixture was stirred at room temperature for 2 h and then the reaction was quenched with water (500 mL). The reaction mixture was extracted with dichloromethane (3 × 500 mL). The organic layers were combined and concentrated under reduced pressure. Purification of the residue by rapid column chromatography on silica gel (eluent: ethyl acetate/petroleum ether, 1:50 v/v) afforded 3,5-dibromo-2-chloropyrazine (90d) as a colorless oil (210 g, 83% yield). Mass spectrum (LCMS, ESI positive ion mode): calculated value C4HBr2ClN2 [M+H]+: 272.8, measured value: 272.6.
