Hydrochloric Acid → HCID 11124334, compound

HRID 1019386Notes

Reaction equation

HRID 1019386 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:20]([C:21]([O:23][CH3:24])=[O:22])=[C:19]([C:25]3[CH:30]=[C:29]([O:31][CH3:32])[C:28]([O:33][CH3:34])=[C:27]([O:35][CH3:36])[CH:26]=3)[C:18]3[C:13](=[CH:14][C:15]([O:39][CH3:40])=[C:16]([O:37][CH3:38])[CH:17]=3)[C:12]2=[O:41])=[CH:7][CH:6]=1)(=O)C.[H-].[Na+].CI.Cl>O1CCCC1.C(Cl)(Cl)Cl>[CH3:38][O:37][C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][C:15]=1[O:39][CH3:40])[C:12](=[O:41])[N:11]([C:8]1[CH:9]=[CH:10][C:5]([NH:4][CH3:1])=[CH:6][CH:7]=1)[C:20]([C:21]([O:23][CH3:24])=[O:22])=[C:19]2[C:25]1[CH:30]=[C:29]([O:31][CH3:32])[C:28]([O:33][CH3:34])=[C:27]([O:35][CH3:36])[CH:26]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 11124582HCID 11124582, compound

Product 1

HCID 11124334HCID 11124334, compoundYield 68.8%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the compound obtained in Example 94 (260 mg) in tetrahydrofuran (3 ml) is added 60% sodium hydride (28 mg) under ice-cooling, and the mixture is stirred at room temperature for 30 minutes. To the reaction mixture is added dropwise methyl iodide (58 μl), and the mixture is stirred for five hours. To the reaction mixture are added dilute hydrochloric acid and chloroform. The chloroform layer is separated, washed, dried, and concentrated under reduced pressure. To the residue is added a mixture of methanol and 2M hydrochloric acid (1:1) (10 ml), and the mixture is heated under reflux for 16 hours. The reaction mixture is cooled to room temperature, and concentrated under reduced pressure to remove the methanol. To the resulting aqueous layer is added aqueous sodium hydrogen carbonate solution to adjust the pH value to pH 8. The mixture is extracted with chloroform. The extract is washed with water, dried, and concentrated under reduced pressure. The residue is crystallized from diethyl ether to give 6,7-dimethoxy-3-methoxycarbonyl-2-[4-(methylamino)phenyl]-4-(3,4,5-trimethoxyphenyl)-1(2H)-isoquinolinone (170 mg) as listed in Table 7.

Workup

  1. temperaturecooling
  2. stirringthe mixture is stirred for five hours
  3. customThe chloroform layer is separated
  4. washwashed
  5. customdried
  6. concentrationconcentrated under reduced pressure
  7. additionTo the residue is added
  8. additiona mixture of methanol and 2M hydrochloric acid (1:1) (10 ml)
  9. temperaturethe mixture is heated
  10. temperatureunder reflux for 16 hours
  11. temperatureThe reaction mixture is cooled to room temperature
  12. concentrationconcentrated under reduced pressure
  13. customto remove the methanol
  14. additionTo the resulting aqueous layer is added aqueous sodium hydrogen carbonate solution
  15. extractionThe mixture is extracted with chloroform
  16. washThe extract is washed with water
  17. customdried
  18. concentrationconcentrated under reduced pressure
  19. customThe residue is crystallized from diethyl ether

Sources & evidence

ORD record
ord-8554b048ebfe495db51f81452557af1d
Source dataset
uspto-grants-2002_11
Patent number
US06486155B1

Reaction notes

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