d) Synthesis of methyl 6-amino-5-bromopyridine-2-carboxylate: Methyl 6-aminopyridine-2-carboxylate (10 g, 66.0 mmol) was dissolved in chloroform (450 mL) at room temperature, and a chloroform (100 mL) solution of bromine (3.4 mL, 66.0 mmol) was slowly added. The reaction mixture was stirred for 40 hours, then diluted with chloroform and washed sequentially with saturated sodium thiosulfate solution and water. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using ethyl acetate/hexane as eluent to afford methyl 5-bromo-6-aminopyridine-2-carboxylate as a yellow solid (3.3 g, 22% yield).MS ESI (m/e): 231.0 [(M + H)+].1H NMR (CDCl3, 400 MHz): δ ( ppm) = 7.76 (d, J = 7.88 Hz, 1H), 7.34 (d, J = 7.92 Hz, 1H), 5.23 (s, 2H), 3.94 (s, 3H).
(d) Isolation of methyl 6-amino-3-bromopyridine-2-carboxylate: In step d), the isomer methyl 6-amino-3-bromopyridine-2-carboxylate was isolated as a by-product to give methyl 6-amino-3-bromopyridine-2-carboxylate (3.0 g, 19% yield).MS ESI (m/e): 231.2 [(M + H)+].1H NMR (CDCl3, 400 MHz): δ (ppm) = 7.60 (d , J = 8.72 Hz, 1H), 6.47 (d, J = 7.88 Hz, 1H), 4.71 (s, 2H), 3.94 (s, 3H).
