The general procedure for the synthesis of 4-amino-3-bromo-5-nitropyridine from 4-amino-3-nitropyridine was as follows: 3-nitropyridin-4-amine (LXVIII) (10 g, 71.88 mmol) was mixed with acetic acid (100 ml) in a sealed tube, followed by the addition of sodium acetate (NaOAc) (29.50 g, 359 mmol), and the slow dropwise addition of bromine ( 4.43 ml, 86.3 mmol). The sealed tube was heated at 100 °C for overnight reaction under stirring conditions. Upon completion of the reaction, the mixture was concentrated under vacuum and the resulting solid was dissolved in water, alkalized with saturated aqueous sodium bicarbonate (NaHCO3) and extracted with dichloromethane (DCM). The organic phases were combined, dried and concentrated to give 3-bromo-5-nitropyridin-4-amine (LXIX) as a yellow solid (13.7 g, 62.8 mmol, 87% yield). The product was identified by 1H NMR (DMSO-d6, 500 MHz): δ 8.58 (s, 1H), 9.19 (s, 1H); ESIMS analysis showed the molecular ion peak m/z 218.1 (M + H), corresponding to the molecular formula C5H4BrN3O2.
