[NH3:1].CO.Br[CH2:5][C:6]1[C:7]([F:23])=[C:8]([O:13][C:14]2[CH:15]=[C:16]([CH:19]=[C:20]([Cl:22])[CH:21]=2)[C:17]#[N:18])[C:9]([F:12])=[CH:10][CH:11]=1>C1COCC1>[NH2:1][CH2:5][C:6]1[C:7]([F:23])=[C:8]([O:13][C:14]2[CH:15]=[C:16]([CH:19]=[C:20]([Cl:22])[CH:21]=2)[C:17]#[N:18])[C:9]([F:12])=[CH:10][CH:11]=1A 7M solution of ammonia in MeOH (45.8 mL, 321 mmol) was added to a solution of 3-{[3-(bromomethyl)-2,6-difluorophenyl]oxy}-5-chlorobenzonitrile (2.3 g, 6.41 mmol) in THF (30 mL) at RT. The reaction was capped and stirred for 16 h at RT then concentrated to dryness under vacuum. Ethyl acetate (200 mL) and saturated aqueous NaHCO3 solution (300 mL) were added. The organic layer was separated, washed with saturated aqueous NaHCO3 solution (2×200 mL), water (200 mL), brine (200 mL), dried over Na2SO4, filtered and concentrated to give a white solid. The crude product was purified on silica gel (10% MeOH/DCM) to give the title compound (1.63 g, 86%) as a white solid (N4011-13-100). 1H NMR (400 MHz, DMSO-d5) δ ppm 7.82 (s, 1H), 7.40-7.66 (m, 3H), 7.31 (t, 1H), 3.75 (s, 2H), 1.86 (br. s., 2H).
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