239122-51-1

74266-66-3

239122-51-1

Intermediate 25A: Preparation of 5-bromo-3-fluoro-2-methoxyaniline 5-Bromo-1-fluoro-2-methoxy-3-nitrobenzene (1.0 g, 4.0 mmol), zinc powder (2.62 g, 40.0 mmol) and ammonium chloride (2.14 g, 40.0 mmol) were dissolved in a mixed solvent of ethanol (20 mL) and water (12 mL). The reaction mixture was heated at 80 °C for 10 minutes, followed by stirring at room temperature for 2 hours. Upon completion of the reaction, the reaction mixture was diluted with dichloromethane (100 mL) and water (60 mL) and filtered through diatomaceous earth (CELITE). The organic phase was separated, dried over anhydrous sodium sulfate, filtered and concentrated to give Intermediate 25A (723 mg, 82% yield) as a gray solid. HPLC analytical conditions: Phenomenex Luna 5 μm C18 column (4.6×30 mm), mobile phase 10-90% aqueous methanol containing 0.1% TFA, 2-minute gradient, flow rate of 5 mL/min, detection wavelength 254 nm, retention time (Rt) = 1.3 min. Mass spectrum (electrospray ionization, ES): m/z = 222.0 [M + H]+.