1187449-01-9

84249-14-9

1187449-01-9

General procedure for the synthesis of 4-bromo-5-chloro-2-aminopyridine from 2-amino-4-bromopyridine: [00252] Synthesis of 4-bromo-5-chloropyridin-2-amine: to a stirred solution of 4-bromopyridin-2-amine (30.0 g, 173 mmol) in DMF (350 mL) was slowly added 1-chloropyrrolidine-2,5-dione at -20 °C ( 24.3 g, 182 mmol). The reaction mixture was stirred continuously at room temperature for 24 hours. Upon completion of the reaction, the mixture was slowly poured into pre-cooled aqueous 1 M NaOH solution (300 mL). Extraction was carried out with ether (2 x 400 mL), the organic phases were combined and washed sequentially with water (3 x 200 mL), brine (200 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by recrystallization from dichloromethane to afford the target compound 27A as a red solid (22.0 g, 106 mmol, 61% yield).LC-MS analysis: the theoretical molecular weight of C5H4BrClN2 was 205.93, and the measured [M + H]+ was 206.9.