Hydrochloric Acid → HCID 18976200, compound

HRID 2393616Notes

Reaction equation

HRID 2393616 reaction equation
[C:1]([CH2:3][CH2:4][C:5]1([NH:24][C:25]([C:27]2[N:28]=[CH:29][C:30]3[C:35]([CH:36]=2)=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:26])[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH3:15])[CH:12]=2)[N:7]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[C:6]1=[O:23])#N.Cl.[OH2:38].[CH3:39][OH:40]>>[F:22][C:19]1[CH:18]=[CH:17][C:16]([N:7]2[C:8]3[C:13](=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=3)[C:5]([CH2:4][CH2:3][C:1]([O:40][CH3:39])=[O:38])([NH:24][C:25]([C:27]3[N:28]=[CH:29][C:30]4[C:35]([CH:36]=3)=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:26])[C:6]2=[O:23])=[CH:21][CH:20]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 962WaterHCID 18976224HCID 18976224, compound

Product 1

HCID 18976200HCID 18976200, compound

Procedure

160 g of (+)-N-[3-(2-cyanoethyl)-1-(4-fluorophenyl)-2,3-dihydro-5-methoxy-2-oxo-1H-indol-3-yl]-3-isoquinolinecarboxamide was dissolved in 770 ml of methyl alcohol, and under ice cooling, a hydrochloric acid gas was passed through the solution for about 2 hours. Then, 6.6 ml of water was added, and the whole mixture was refluxed under heating for 1 hour. After returning to room temperature, the reaction mixture was concentrated under reduced pressure and diluted with an aqueous sodium hydrogen carbonate solution and ethyl acetate, and the organic layer was collected by separation. This organic layer was washed with water with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate and filtered, and the solvent was removed by evaporation under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate: n-hexane =1:2 to 1:1) to afford (+)-methyl 3-[l-(4-fluorophenyl)-2,3-dihydro-3-(3-isoquinolinyl)carbonylamino-5-methoxy-2-oxo-1H-indol-3-yl]propionate as an amorphous substance. [α]D25 : +7.25° (c=0.248, methanol).

Workup

  1. temperaturethe whole mixture was refluxed
  2. temperatureunder heating for 1 hour
  3. customAfter returning to room temperature
  4. concentrationthe reaction mixture was concentrated under reduced pressure
  5. additiondiluted with an aqueous sodium hydrogen carbonate solution and ethyl acetate
  6. customthe organic layer was collected by separation
  7. washThis organic layer was washed with water with a saturated sodium chloride solution
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customthe solvent was removed by evaporation under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (ethyl acetate: n-hexane =1:2 to 1:1)

Sources & evidence

ORD record
ord-426af8515d5745d8a6b89ff072d35268
Source dataset
uspto-grants-1998_09
Patent number
US05807883

Reaction notes

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