Water → HCID 18368016, compound

HRID 379842Notes

Reaction equation

HRID 379842 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([Cl:11])=[CH:8][CH:9]=2)[NH:4][C:3]=1[C:12](=[O:27])[C:13]1[CH:18]=[CH:17][C:16]([O:19]COC)=[C:15]([O:23]COC)[CH:14]=1.[C:28](Cl)(=[O:30])[CH3:29].O>N1C=CC=CC=1.ClCCl>[C:28]([NH:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([Cl:11])=[CH:8][CH:9]=2)[NH:4][C:3]=1[C:12](=[O:27])[C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[C:15]([OH:23])[CH:14]=1)(=[O:30])[CH3:29]

Participants

6

Reactant 3

HCID 962WaterHCID 6367Acetyl chlorideHCID 18367927HCID 18367927, compound

Product 1

HCID 18368016HCID 18368016, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-amino-6-chloro-2-[[3,4-bis(methoxymethyloxy)]benzoyl]indole (step 3, 0.50 g, 1.3 mmol) in pyridine (1.0 ml) and dichloromethane (20 ml) cooled to 0° C. was added acetyl chloride (0.10 ml, 1.40 mmol). After stiiring for 1 h at room temperature, the reaction mixture was poured into water (20 ml) and extracted with dichloromethane (30 ml×2). The organic extracts were dried (MgSO4) and solvent removed by evaporation. The residue was dissolved in dichloromethane (30 ml), trifluoroacetic acid (0.50 ml) added and the mixture heated at reflux for 5 h. The mixture was cooled, poured into water and extracted with ethyl acetate (80 ml×2). The organic extracts were dried (MgSO4) and solvent removed by evaporation. The residual oil was purified by flash column chromatography eluting with hexane/ethyl acetate (1/3) to give 80 mg (20%) of the title compound. Recrystallization from ethyl acetate/hexane afforded the title compound as a yellow solid. m.p.: 193-200° C. 1H-NMR (CDCl3) δ: 11.64 (1H, br s), 9.66 (1H, br s), 7.58 (1H, d, J=8.4 Hz), 7.41 (1H, J=1.5 Hz), 7.24 (1H, d, J=2.2 Hz), 7.15 (1H, dd, J=8.8, 1.8 Hz), 7.08 (1H, dd, J=8.8, 1.5 Hz), 6.80 (1H, d, J=8.4 Hz), 1.98 (3H, s)

Workup

  1. extractionextracted with dichloromethane (30 ml×2)
  2. dry with materialThe organic extracts were dried (MgSO4) and solvent
  3. customremoved by evaporation
  4. dissolutionThe residue was dissolved in dichloromethane (30 ml)
  5. additiontrifluoroacetic acid (0.50 ml) added
  6. temperaturethe mixture heated
  7. temperatureat reflux for 5 h
  8. temperatureThe mixture was cooled
  9. additionpoured into water
  10. extractionextracted with ethyl acetate (80 ml×2)
  11. dry with materialThe organic extracts were dried (MgSO4) and solvent
  12. customremoved by evaporation
  13. customThe residual oil was purified by flash column chromatography
  14. washeluting with hexane/ethyl acetate (1/3)

Sources & evidence

ORD record
ord-640a8a9397574015af1f83dcc564e2b8
Source dataset
uspto-grants-2001_10
Patent number
US06300363B1

Reaction notes

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