3-Acetamidophthalic Anhydride → N-{2-[1-(3-cyclopropylmethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-acetamide

HRID 913196Notes

Reaction equation

HRID 913196 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([CH:14]([NH2:20])[CH2:15][S:16]([CH3:19])(=[O:18])=[O:17])[CH:9]=[CH:10][C:11]=2[O:12][CH3:13])[CH2:3][CH2:2]1.[C:21]([NH:24][C:25]1[CH:35]=[CH:34][CH:33]=[C:27]2[C:28]([O:30][C:31](=O)[C:26]=12)=[O:29])(=[O:23])[CH3:22].C([O-])(=O)C.[Na+]>C(O)(=O)C>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([CH:14]([N:20]3[C:31](=[O:30])[C:26]4[C:27](=[CH:33][CH:34]=[CH:35][C:25]=4[NH:24][C:21](=[O:23])[CH3:22])[C:28]3=[O:29])[CH2:15][S:16]([CH3:19])(=[O:17])=[O:18])[CH:9]=[CH:10][C:11]=2[O:12][CH3:13])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 2261213-Acetamidophthalic AnhydrideHCID 517045Sodium AcetateHCID 674176041-(3-Cyclopropylmethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamine

Product 1

HCID 11627237N-{2-[1-(3-cyclopropylmethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-acetamideYield 21.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of 1-(3-cyclopropylmethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamine (1.0 g, 3.3 mmol) in acetic acid (10 mL), was added 3-acetamido-phthalic anhydride (1.37 g, 6.7 mmol) and sodium acetate (0.54 g, 6.7 mmol). The mixture was heated at reflux temperature overnight. The solvent was removed in vacuo. The resulted oil was extracted with ethyl acetate (50 mL) and water (30 mL). The organic layer was washed with water (30 mL×2) and brine (30 mL) and dried over magnesium sulfate. The solvent was removed in vacuo and the resulted oil was purified by silica gel column to give N-{2-[1-(3-cyclopropylmethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-acetamide as a white solid (340 mg, 21%): mp 102-104° C.; 1H NMR (CDCl3) δ 0.35-0.37 (m, 2H, c-CH2), 0.62-0.67 (m, 2H, c-CH2), 0.88-0.93 (m, 2H, c-CH2), 1.25-1.32 (m, 1H, c-CH), 2.25 (s, 3H, CH3), 2.87 (s, 3H, CH3), 3.75 (dd, J=4, 15 Hz, 1H, CHH), 3.83-3.85 (m, 5H, OCH2+OCH3), 4.53 (dd, J=10, 15 Hz, 1H, CH2), 5.85 (dd, J=4, 10 Hz, 1H, NCH), 6.84 (d, J=8 Hz, 1H, Ar), 7.07-7.10 (m, 2H, Ar), 7.45 (d, J=5 Hz, 1H, Ar), 7.62 (t, J=8 Hz, 1H, Ar), 8.72 (d, J=8 Hz, 1H, Ar), 9.45 (s, 1H, NHCO); 13C NMR (CDCl3) δ 1.6, 3.2, 3.3, 24.7, 41.4, 48.3, 54.2, 55.8, 73.9, 111.5, 113.1, 115.0, 118.0, 120.3, 124.7, 129.1, 130.9, 135.9, 137.2, 148.6, 149.8, 167.2, 169.0, 169.3. Analy. Calculated for C24H26N2O7S: C, 59.25; H, 5.39; N, 5.76. Found: C, 59.00; H, 5.36; N, 5.55.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux temperature overnight
  3. customThe solvent was removed in vacuo
  4. extractionThe resulted oil was extracted with ethyl acetate (50 mL) and water (30 mL)
  5. washThe organic layer was washed with water (30 mL×2) and brine (30 mL)
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. customthe resulted oil was purified by silica gel column

Sources & evidence

ORD record
ord-bc0a3fef33fa4656bacb7c6417345bc1
Source dataset
uspto-grants-2011_09
Patent number
US08026269B2

Reaction notes

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