反应详情

温度

65 °C

To a solution of N2-(3-cyanomethyl-2,4,6-trimethylphenyl)-3-[N-(3,4-dimethylisoxazol-5-yl)-N-methoxymethylaminosulfonyl]-2-thiophenecarboxamide (2.29 g, 4.56 mmol) in THF (10 mL) was added concentrated hydrochloric acid (5 mL). The reaction was heated at 65° C. for 2 hours, then allowed to cool to room temperature. The mixture was poured into ice water (100 mL), extracted with ethyl acetate (3×100 mL), washed with saturated sodium chloride (150 mL), dried (MgSO4), then concentrated. The residue was purified by reverse-phase HPLC (20-80% acetonitrile in water). Acetonitrile was removed in vacuo. The aqueous layer was extracted with ethyl acetate (3×100 mL). The extracts were combined and washed with saturated sodium chloride (200 mL), then with saturated sodium bicarbonate (3×200 mL). The organic layer was washed with saturated sodium chloride (200 mL), dried (MgSO4), then concentrated. The residue was purified by reverse-phase HPLC (20-80% acetonitrile in water). Acetonitrile was removed in vacuo. The aqueous layer was extracted with ethyl acetate (3×100 mL). The extracts were combined and washed with saturated sodium chloride (200 mL), then with saturated sodium bicarbonate (3×200 mL). The organic layer was washed with saturated sodium chloride (200 mL), dried (MgSO4), then concentrated. The residue was dissolved in water (300 mL) and lyophilized to give N2-(3-cyanomethyl-2,4,6-trimethylphenyl)-3-[(3,4-dimethyl-5-isoxazolyl)sulfamoyl]-2-thiophenecarboxamide, Na-salt (0.45 g, 21%) as a white powder, mp 153-173° C. 1H NMR (400 MHZ, DMSO-d6δ7.69 (d, J=4.76 Hz, 1H), 7.35 (d, J=5.16 Hz, 1H), 7.02 (s, 1H), 3.90 (s, 2H), 2.32 (s, 3H), 2.20 (s, 3H), 2.13 (s, 3H), 1.95 (s, 3H), 1.55 (s, 3H) IR (KBr) 3449, 2249, 1623, 1421, 1121 cm−1.

1. temperatureto cool to room temperature
2. extractionextracted with ethyl acetate (3×100 mL)
3. washwashed with saturated sodium chloride (150 mL)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated
6. customThe residue was purified by reverse-phase HPLC (20-80% acetonitrile in water)
7. customAcetonitrile was removed in vacuo
8. extractionThe aqueous layer was extracted with ethyl acetate (3×100 mL)
9. washwashed with saturated sodium chloride (200 mL)
10. washThe organic layer was washed with saturated sodium chloride (200 mL)
11. dry with materialdried (MgSO4)
12. concentrationconcentrated
13. customThe residue was purified by reverse-phase HPLC (20-80% acetonitrile in water)
14. customAcetonitrile was removed in vacuo
15. extractionThe aqueous layer was extracted with ethyl acetate (3×100 mL)
16. washwashed with saturated sodium chloride (200 mL)
17. washThe organic layer was washed with saturated sodium chloride (200 mL)
18. dry with materialdried (MgSO4)
19. concentrationconcentrated
20. dissolutionThe residue was dissolved in water (300 mL)