反应详情

To a solution of 4-(2-fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid (70 mg, 0.176 mmol) and O-cyclopropylmethyl-hydroxylamine (23 mg, 0.21 mmol) in DMF (3 mL) was added EDCI (40 mg, 0.21 mmol), HOBt (28 mg, 0.21 mmol) and DIPEA (70 μL, 0.42 mmol). The reaction mixture was stirred at room temperature for 18 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 solid was triturated with a solution of hot methanol/water/NaHCO3, the solid filtered off, washed with water to give the title compound as a pale pink solid (24 mg, 29%). LCMS (Method A): RT=10.42 min, [M+H]+=467. 1H NMR (DMSO-d6, 400 MHz) 13.17 (1 H, s), 7.64 (1 H, dd, J=10.37, 1.95 Hz), 7.48 (1 H, d, J=8.76 Hz), 7.42-7.37 (1 H, m), 7.26 (1 H, d, J=0.95 Hz), 7.01 (1 H, dd, J=8.76, 0.99 Hz), 6.87 (1 H, t, J=8.66 Hz), 3.62 (2 H, d, J=7.13 Hz), 1.08-1.00 (1 H, m), 0.50-0.44 (2 H, m), 0.23-0.17 (2 H, m).

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 with a solution of hot methanol/water/NaHCO3
6. filtrationthe solid filtered off
7. washwashed with water