反应详情

To a solution of 4-(2-fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid (100 mg, 0.252 mmol) in DMF (3 mL) was added 0-(tetrahydro-pyran-4-yl)-hydroxylamine (44 mg, 0.378 mmol), HOBt (37 mg, 0.277 mmol), EDCI (53 mg, 0.277 mmol) and DIPEA (92 μl, 0.529 mmol). The reaction was stirred at room temperature for 70 hours. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate then water, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 30-100% ethyl acetate in cyclohexane). The resultant solid was triturated in methanol, the solid filtered off, washed with methanol to yield the title compound (33 mg, 26%). LCMS (Method A): RT=9.27 min, [M+H]+=497. 1H NMR (DMSO-d6, 400 MHz): 13.19 (1 H, s), 11.44 (1 H, s), 9.87 (1 H, s), 7.65 (1 H, dd, J=10.36, 1.95 Hz), 7.48 (1H, d, J=8.77 Hz), 7.44-7.38 (1H, m), 7.28 (1 H, s), 7.03 (1 H, d, J=8.75 Hz), 6.89 (1 H, t, J=8.66 Hz), 4.02-3.93 (1 H, m), 3.84-3.76 (2 H, m), 3.36-3.28 (2 H, m), 1.88-1.81 (2 H, m), 1.51 (2 H, dddd, J=12.96, 9.42, 8.75, 4.11 Hz).

1. washwashed with saturated aqueous sodium hydrogen carbonate
2. dry with materialwater, dried (Na2SO4)
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customThe resultant solid was triturated in methanol
6. filtrationthe solid filtered off
7. washwashed with methanol