The general procedure for the synthesis of 2-amino-5-bromo-6-methoxypyridine from methanol and 5,6-dibromopyridin-2-amine was as follows: sodium metal (1.8 g, 78.2 mmol) was added in small portions to dry methanol (70 mL) at -20 °C. The resulting solution was stirred at 0 °C for 4 hours. Subsequently, the reaction mixture was transferred to a sealed tube, 5,6-dibromopyridin-2-amine (Example 7a, 10 g, 39.8 mmol) was added and heated at 120 °C for 24 hours. After completion of the reaction, the solvent was removed under reduced pressure and the residue was diluted with water. The aqueous phase was neutralized with 2 M HCl and then extracted with ethyl acetate (3 x 100 mL). The organic phases were combined, dried with magnesium sulfate, filtered and concentrated in vacuum. The residue was purified by fast column chromatography using a gradient elution with a hexane solution of 5% to 15% acetone to afford the target product 2-amino-5-bromo-6-methoxypyridine (6.6 g, 82% yield). The product was confirmed by 1H NMR (400 MHz, CDCl3): δ 3.91 (s, 3H), 4.31 (br. s., 2H), 5.99 (d, 1H), 7.48 (d, 1H). esms m/z 202.8, 204.8 [M + H]+.
