Water → HCID 22175494, compound

HRID 1797484Notes

Reaction equation

HRID 1797484 reaction equation
[CH2:1]([O:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([Cl:17])=[C:13]([Cl:16])[CH:14]=2)[C:9](=[O:18])[N:8]([CH2:19][CH2:20]C(O)=O)[C:7]=1[CH2:24][N:25]1[C:33](=[O:34])[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]1=[O:35])[CH2:2][CH2:3][CH3:4].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C([N:55]([CH2:58]C)CC)C.[OH2:60].CN(C)[CH:63]=[O:64]>>[CH2:1]([O:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([Cl:17])=[C:13]([Cl:16])[CH:14]=2)[C:9](=[O:18])[N:8]([CH2:19][CH2:20][NH:55][C:58](=[O:60])[O:64][CH3:63])[C:7]=1[CH2:24][N:25]1[C:26](=[O:35])[C:27]2[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:33]1=[O:34])[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 22175773HCID 22175773, compound

Product 1

HCID 22175494HCID 22175494, compoundYield 36.6%

Procedure

A solution of 3-[4-butoxy-6,7-dichloro-3-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-oxo-2(1H)-isoquinolinyl]propionic acid (0.78 g, 1.5 mmol), diphenylphosphoryl azide (0.39 ml, 1.8 mmol) and triethylamine (0.25 ml, 1.8 mmol) in N,N-dimethylformamide (10 ml) was stirred at room temperature for 2 h. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in toluene (20 ml) and the mixture was refluxed with stirring. To the obtained mixture was added methanol (1 ml) and the mixture was refluxed with stirring for 1 h. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from tetrahydrofuran-diisopropyl ether to give methyl 2-[4-butoxy-6,7-dichloro-3-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-oxo-2(1H)-isoquinolinyl]ethylcarbamate (0.30 g, 36.6%) as crystals.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in toluene (20 ml)
  6. temperaturethe mixture was refluxed
  7. additionTo the obtained mixture was added methanol (1 ml)
  8. temperaturethe mixture was refluxed
  9. stirringwith stirring for 1 h
  10. additionThe reaction mixture was poured into water
  11. extractionextracted with ethyl acetate
  12. washThe extract was washed with brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was recrystallized from tetrahydrofuran-diisopropyl ether

Sources & evidence

ORD record
ord-001b4471c2e84489a7bd4ccb3c5ba052
Source dataset
uspto-grants-2006_04
Patent number
US07034039B2

Reaction notes

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