反应详情

温度

80 °C

To a solution of N2-(3-acetoxymethyl-2,4,6-trimethylphenyl)-3-[N-(3,4-dimethylisoxazol-5-yl)-N-methoxymethylaminosulfonyl]-2-thiophenecarboxamide (0.78 g, 1.46 mmol) in acetic acid (7 mL) and water (3 mL) was added 2N sulfuric acid (3 drops). The reaction was heated at 80° C. for 4 hours, then allowed to cool to room temperature. The mixture was poured into ice water (50 mL), extracted with ethyl acetate (3×50 mL), washed with saturated sodium chloride (50 mL), dried (MgSO4), then concentrated. The residue was purified by reverse-phase HPLC (20-80% acetonitrile in water) which gave N2-(3-acetoxymethyl-2,4,6-trimethylphenyl)-3-[(3,4-dimethyl-5-isoxazolyl)sulfamoyl]-2-thiophenecarboxamide (0.2 g, 28%) as an off-white powder, mp 75-77° C. 1H NMR (400 MHZ, DMSO-d6δ7.84 (d, J=5.12 Hz, 1H), 7.34 (d, J=5.12 Hz, 1H), 7.00 (s, 1H), 5.12 (s, 2H), 2.30 (s, 3H), 2.20 (s, 3H), 2.17 (s, 3H), 2.07 (s, 3H), 2.02 (s, 3H), 1.65 (s, 3H) IR (KBr) 3458, 1738, 1646, 1356, 1181 cm−1. And N2-(3-hydroxymethyl-2,4,6-trimethylphenyl)-3-[(3,4-dimethyl-5-isoxazolyl)sulfamoyl]-2-thiophenecarboxamide (45 mg, 6.9%), ratio 4:1 respectively, as a white powder, mp 100-115° C. 1H NMR (400 MHZ, DMSO-d6δ7.84 (3, J=5.12 Hz, 1H), 7.34 (d, J=5.16 Hz, 1H), 6.92 (s, 1H), 4.48 (s, 2H), 2.33 (s, 3H), 2.23 (s, 3H), 2.14 (s, 3H), 2.07 (s, 3H), 1.65 (s, 3H) IR (KBr) 3439, 1651, 1341, 1181 cm−1.

1. temperatureto cool to room temperature
2. extractionextracted with ethyl acetate (3×50 mL)
3. washwashed with saturated sodium chloride (50 mL)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated
6. customThe residue was purified by reverse-phase HPLC (20-80% acetonitrile in water) which