反应详情

To a solution of 4-(2-fluoro-4-iodo-phenylamino)-benzo[d]iso-thiazole-5-carboxylic acid (150 mg, 0.362 mmol), diisopropylethylamine (0.25 mL, 1.45 mmol), HOBt (98 mg, 0.724 mmol) and (S)-1-aminooxy-propan-2-ol (92 mg, 0.724 mmol in DMF (2 mL) was added EDCI (139 mg, 0.724 mmol). The reaction mixture was stirred for 16 hours at room temperature, diluted with ethyl acetate, and washed with water, a saturated aqueous solution of sodium hydrogen carbonate, then brine before being dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 30% to 80%, EtOAc in cyclohexane) to afford the title compound as a solid (45 mg, 26%). LCMS (method A): RT=10.26 min, [M+H]+=488. 1H NMR (DMSO-d6, 400 MHz) 11.72 (1 H, s), 9.22 (1 H, s), 8.69 (1 H, s), 7.86-7.81 (1 H, m), 7.64-7.55 (2 H, m), 7.30 (1 H, dd, J=8.47, 1.83 Hz), 6.63 (1 H, t, J=8.72 Hz), 4.73 (1 H, s), 3.76-3.68 (1 H, m), 3.53 (2 H, d, J=5.78 Hz), 0.99 (3 H, d, J=6.33 Hz).

1. washwashed with water
2. dry with materiala saturated aqueous solution of sodium hydrogen carbonate, then brine before being dried (Na2SO4)
3. filtrationfiltered
4. concentrationconcentrated in vacuo