Hydrochloric Acid → HCID 18976185, compound

HRID 2393611Notes

Reaction equation

HRID 2393611 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][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[N:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[F:22])[C:6]1=[O:23])#N.Cl.[OH2:38].[CH3:39][OH:40]>>[F:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[N:7]1[C:8]2[C:13](=[CH:12][CH:11]=[C:10]([O:14][CH3:15])[CH:9]=2)[C:5]([CH2:4][CH2:3][C:1]([O:40][CH3:39])=[O:38])([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:6]1=[O:23]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 962WaterHCID 18976202HCID 18976202, compound

Product 1

HCID 18976185HCID 18976185, compoundYield 91%

Procedure

In 80 ml of anhydrous methanol was dissolved 23.85 g of the (+)-N-[3-(2-cyanoethyl)-1-(2-fluorophenyl)-2,3-dihydro-6-methoxy-2-oxo-1H-indol-3-yl]-3-isoquinolinecarboxamide crude product, and under ice cooling, a hydrochloric acid gas was passed through the solution until the gas was saturated. Thereafter, 1.71 ml of water was added to the solution. The reaction mixture was refluxed for 1 hour, cooled and then concentrated under reduced pressure. The residue was neutralized with an aqueous saturated sodium hydrogen carbonate solution and then extracted with ethyl acetate. The organic layer was separated, washed with water with a saturated sodium chloride solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (ethyl acetate:hexane (1:1, volume) as an eluant to afford 22.30 g of (+)-methyl 3-[l-(2-fluorophenyl)-2,3-dihydro-3-(3-isoquinolinyl)carbonylamino-6-methoxy-2-oxo-1H-indol-3-yl]propionate as a pale yellow amorphous solid (yield: 91% (from the product of Example 176 (2))). DI-MS (m/z) 513 (MH+), 426, 156, 128 (base). [α]D25 : +66.2° (c=0.402, chloroform).

Workup

  1. temperatureThe reaction mixture was refluxed for 1 hour
  2. temperaturecooled
  3. concentrationconcentrated under reduced pressure
  4. extractionextracted with ethyl acetate
  5. customThe organic layer was separated
  6. washwashed with water with a saturated sodium chloride solution
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationAfter filtration
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customthe resulting residue was purified by silica gel column chromatography (ethyl acetate:hexane (1:1, volume) as an eluant

Sources & evidence

ORD record
ord-c9cccdca3f8b467aace279e6a6d11202
Source dataset
uspto-grants-1998_09
Patent number
US05807883

Reaction notes

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