反应详情

To a solution of 2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-9-(4-fluorophenyl)-8,9-dihydro-5H-[1,2,4]triazolo[1,5-a]azepin-7(6H)-one (100 mg, 0.214 mmol, from example 137) in ethanol (1.1 mL) was added methoxylamine hydrochloride (35.8 mg, 0.428 mmol) and DIPEA (112 μL, 0.643 mmol). The resulting mixture was stirred at rt for 16 h. The reaction mixture was diluted with EtOAc (10 mL), washed with water (5 mL), brine (5 mL), dried over Mg SO4, filtered and concentrated in vacuo. The crude product was purified using reverse phase preparatory HPLC (MeOH/water/trifluoroacetic acid) to afford the TFA salt of the titled compound as a mixture of E/Z isomers (76.7 mg, 56% yield). LC-MS (M+H)+ 496.2. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 9.52-9.79 (1 H, m), 8.02 (1 H, s), 7.25-7.36 (1 H, m), 7.05-7.25 (7 H, m), 4.46-4.73 (3 H, m), 3.81-3.97 (6 H, m), 2.95-3.24 (3 H, m), 2.84 (1 H, t, J=5.8 Hz).

1. washwashed with water (5 mL), brine (5 mL)
2. dry with materialdried over Mg SO4
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customThe crude product was purified