5-Bromo-2-chloropyridine-3-carboxamide

7664-41-7

29241-65-4

75291-85-9

General procedure for the synthesis of 2-chloro-5-bromopyridine-3-carboxamide from ammonia and 5-bromo-2-chloronicotinic acid: 1. 5-bromo-2-chloronicotinic acid (20 g, 84.6 mmol) and oxalyl chloride (12.9 g, 101.5 mmol) were suspended in dichloromethane (500 mL) in a dry reaction flask and N,N-dimethylformamide (618 mg, 8.46 mmol) was added as a catalyst. 2. The reaction mixture was stirred at room temperature for 3 h. The gas generated during the reaction was exhausted by nitrogen purge. Subsequently, the reaction solution was concentrated in vacuum to half of the original volume. 3. At -10°C, the above concentrate was slowly added dropwise to a pre-cooled mixture of 7N methanol ammonia solution (50 mL) and dichloromethane (200 mL). After the dropwise addition was completed, the reaction mixture was transferred to room temperature and stirring was continued for 18 hours. 4. Upon completion of the reaction, the reaction solution was concentrated under vacuum to remove the solvent. The residue was diluted with ethyl acetate (1 L) and then washed with water (500 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated again under vacuum. 5. The solid residue obtained was ground with cold dichloromethane (200 mL) and the solid was collected by filtration to afford 2-chloro-5-bromopyridine-3-carboxamide as a colorless solid (16.3 g, 82% yield). The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 7.81 (s, 1H), 8.08 (s, 1H), 8.21 (d, 1H), 8.63 (d, 1H).