Synthesis
General procedure for the synthesis of 4,6-dichloropyridine-3-amide from 4,6-dichloronicotinic acid: oxalyl chloride (7.70 mL, 88.3 mmol) was slowly added to a suspension of 4,6-dichloronicotinic acid (8.47 g, 44.1 mmol) in dimethylformamide (200 mL) over a period of 1 h. The reaction was carried out at room temperature. After addition, the reaction mixture was continued to be stirred at room temperature for 3 hours, followed by vacuum concentration. The residue was dissolved in dichloromethane (200 mL), followed by the slow dropwise addition of ammonia (8.3 mL, 130 mmol) over a period of 30 minutes [Note: the addition of ammonia triggers an exothermic reaction, and the rate of dropwise acceleration needs to be controlled to ensure that the reaction temperature does not exceed 25°C]. After dropwise addition, the reaction mixture was continued to be stirred at room temperature for 1 hour, after which it was diluted with water (600 mL) and extracted with ethyl acetate (4 x 600 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated to afford 4,6-dichloropyridin-3-amide as a light brown solid (8.05 g, 95% yield). The product was used for subsequent reactions without further purification.1H NMR (400 MHz, d6-DMSO) δ 8.48 (s, 1H), 8.10 (br s, 1H), 7.87 (br s, 2H).
References
[1] Patent: US2015/291629, 2015, A1. Location in patent: Paragraph 1173-1174
[2] Patent: US2006/217417, 2006, A1. Location in patent: Page/Page column 12; 13
