Sodium Hydroxide → HCID 22048365, compound

HRID 1833176Notes

Reaction equation

HRID 1833176 reaction equation
C([O:3][C:4]([C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:24][CH3:25])=[C:13]([O:16][CH2:17][CH2:18][N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)[CH:14]=2)[C:9]([C:26](=[O:37])[C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH:34]([CH3:36])[CH3:35])[CH:28]=2)=[N:8][CH:7]=1)=[O:5])C.[OH-].[Na+]>C(O)C.O1CCCC1>[CH:34]([O:33][C:29]1[CH:28]=[C:27]([CH:32]=[CH:31][CH:30]=1)[C:26]([C:9]1[C:10]2[C:15](=[CH:14][C:13]([O:16][CH2:17][CH2:18][N:19]3[CH2:20][CH2:21][CH2:22][CH2:23]3)=[C:12]([O:24][CH3:25])[CH:11]=2)[C:6]([C:4]([OH:5])=[O:3])=[CH:7][N:8]=1)=[O:37])([CH3:36])[CH3:35]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 69558488HCID 69558488, compound

Product 1

HCID 22048365HCID 22048365, compoundYield 41.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 6-hydroxy-1-(3-isopropoxy-benzoyl)-7-methoxy-isoquinoline-4-carboxylic acid ethyl ester (70 mg, 0.17 mmol) in N,N dimethylformamide (2 mL) was added potassium carbonate (237 mg, 1.71 mmol) and 2-chloro-N,N-dimethyl-acetamide (0.088 mL, 0.86 mmol) at room temperature. The reaction mixture was heated 85° C. for 2 hrs. The solvent was evaporated and the crude product was diluted with ethyl acetate and water. The aqueous phase was extracted with ethyl acetate (3×20 mL). The combined extracts were washed with saturated aqueous sodium chloride solution (20 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70–230 mesh, 30% ethyl acetate/hexane) afforded 6-dimethylcarbamoylmethoxy-1-(3-isopropoxy-benzoyl)-7-methoxy-isoquinoline-4-carboxylic acid ethyl ester. To a stirred solution of 1-(3-isopropoxy-benzoyl)-7-methoxy-6-(2-pyrrolidin-1-yl-ethoxy)-isoquinoline-4-carboxylic acid ethyl ester (73.0 mg, 0.14 mmol) in ethanol (1.0 mL) and tetrahydrofuran (0.5 mL) was added 4N aqueous sodium hydroxide (0.144 mL, 0.56 mmol) at room temperature. The mixture was heated at 60° C. for 1 h. The solvent was evaporated and the residue was diluted with dichloromethane and water. The aqueous phase was acidified to pH=3 by addition of 1N hydrochloride solution and then was extracted with dichloromethane (3×20 mL). The combined extracts were washed with saturated aqueous sodium chloride solution (20 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The crude product recrystallized from ethyl acetate to afford 1-(3-isopropoxy-benzoyl)-7-methoxy-6-(2-pyrrolidin-1-yl-ethoxy)-isoquinoline-4-carboxylic acid as a light brown solid (28 mg, 37% yield). HR-MS m/e calcd for C23H21N1O6 (M−H+) 440.1340, found 440.1347; 1H NMR (300 MHz) compatible.

Workup

  1. customThe solvent was evaporated
  2. additionthe residue was diluted with dichloromethane and water
  3. additionThe aqueous phase was acidified to pH=3 by addition of 1N hydrochloride solution
  4. extractionwas extracted with dichloromethane (3×20 mL)
  5. washThe combined extracts were washed with saturated aqueous sodium chloride solution (20 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-25a9d8e44b2a477ea9281b64427bd47d
Source dataset
uspto-grants-2006_06
Patent number
US07067529B2

Reaction notes

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