N2-(3-acetoxymethyl-2,4,6-trimethylphenyl)-3-[N-(3,4-dimethylisoxazol-5-yl)-N-methoxymethylaminosulfonyl]-2-thiophenecarboxamide → N2-(3-acetoxymethyl-2,4,6-trimethylphenyl)-3-[(3,4-dimethyl-5-isoxazolyl)sulfamoyl]-2-thiophenecarboxamide

HRID 2229922Notes

Reaction equation

HRID 2229922 reaction equation
[C:1]([O:4][CH2:5][C:6]1[C:7]([CH3:36])=[C:8]([NH:14][C:15]([C:17]2[S:18][CH:19]=[CH:20][C:21]=2[S:22]([N:25]([C:29]2[O:33][N:32]=[C:31]([CH3:34])[C:30]=2[CH3:35])COC)(=[O:24])=[O:23])=[O:16])[C:9]([CH3:13])=[CH:10][C:11]=1[CH3:12])(=[O:3])[CH3:2]>C(O)(=O)C.O.S(=O)(=O)(O)O>[C:1]([O:4][CH2:5][C:6]1[C:7]([CH3:36])=[C:8]([NH:14][C:15]([C:17]2[S:18][CH:19]=[CH:20][C:21]=2[S:22](=[O:24])(=[O:23])[NH:25][C:29]2[O:33][N:32]=[C:31]([CH3:34])[C:30]=2[CH3:35])=[O:16])[C:9]([CH3:13])=[CH:10][C:11]=1[CH3:12])(=[O:3])[CH3:2]

Participants

5

Reactant 1

HCID 54548392N2-(3-acetoxymethyl-2,4,6-trimethylphenyl)-3-[N-(3,4-dimethylisoxazol-5-yl)-N-methoxymethylaminosulfonyl]-2-thiophenecarboxamide

Product 1

HCID 10553132N2-(3-acetoxymethyl-2,4,6-trimethylphenyl)-3-[(3,4-dimethyl-5-isoxazolyl)sulfamoyl]-2-thiophenecarboxamideYield 28%

Reagents, catalysts & solvents 3

HCID 1118Sulfuric AcidCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-bddc1d4981554cf19b26f467affcd377
Source dataset
uspto-grants-2002_07
Patent number
US06420567B1

Reaction notes

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