Water → 3-(4-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)phenyl)-7-methoxyisoquinolin-1(2H)-one

HRID 333675Notes

Reaction equation

HRID 333675 reaction equation
CS([O:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][N:17]=[N+:18]=[N-:19])(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+].O[C:27]1[CH:32]=[CH:31][C:30]([C:33]2[NH:34][C:35](=[O:45])[C:36]3[C:41]([CH:42]=2)=[CH:40][CH:39]=[C:38]([O:43][CH3:44])[CH:37]=3)=[CH:29][CH:28]=1.O>CN(C=O)C>[N:17]([CH2:16][CH2:15][O:14][CH2:13][CH2:12][O:11][CH2:10][CH2:9][O:8][CH2:7][CH2:6][O:5][C:27]1[CH:28]=[CH:29][C:30]([C:33]2[NH:34][C:35](=[O:45])[C:36]3[C:41]([CH:42]=2)=[CH:40][CH:39]=[C:38]([O:43][CH3:44])[CH:37]=3)=[CH:31][CH:32]=1)=[N+:18]=[N-:19]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 148276732-(2-(2-(2-Azidoethoxy)ethoxy)ethoxy)ethyl methanesulfonateHCID 533793633-(4-hydroxyphenyl)-7-methoxyisoquinolin-1(2H)-one2×

Product 1

HCID 866809733-(4-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)phenyl)-7-methoxyisoquinolin-1(2H)-oneYield 23.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl methanesulphonate (175 mg, 0.58 mmol) and Cs2CO3 (190 mg, 0.58 mmol) are added to a mixture of 3-(4-hydroxyphenyl)-7-methoxyisoquinolin-1(2H)-one (compound 45) (130 mg, 0.48 mmol) in DMF (6 mL). The reaction mixture is heated at 80° C. for 24 hours. Then the solvent is evaporated off, the reaction crude is added to water (100 mL) and extracted with CH2Cl2 (3×100 mL). The organic phase is dried over MgSO4, filtered and concentrated under reduced pressure. The residue obtained is purified by chromatography on a silica column using a gradient of EtOH (1 to 3%) in CH2Cl2 as eluents. Intermediate 3-(4-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)phenyl)-7-methoxyisoquinolin-1(2H)-one (52 mg, 23%) is obtained, which is used directly in the following stage.

Workup

  1. customThen the solvent is evaporated off
  2. customthe reaction crude
  3. extractionextracted with CH2Cl2 (3×100 mL)
  4. dry with materialThe organic phase is dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue obtained
  8. customis purified by chromatography on a silica column

Sources & evidence

ORD record
ord-986d7ccab09b48e482ece32d364ac263
Source dataset
uspto-grants-2014_11
Patent number
US08883763B2

Reaction notes

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