Hydrochloric Acid → N2-(3-cyanomethyl-2,4,6-trimethylphenyl)-3-[(3,4-dimethyl-5-isoxazolyl)sulfamoyl]-2-thiophenecarboxamide

Participants

Reaction Conditions

Reaction Steps

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-d6) δ7.69 (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) ppm. IR (KBr) 3449, 2249, 1623, 1421, 1121 cm−1.

Provenance & Evidence