Methylhydrazine → 6-chloro-2-methylamino-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl Ester

HRID 750126Notes

Reaction equation

HRID 750126 reaction equation
[CH3:1][O:2][C:3]([C:5]1[O:6][C:7]([C:9]2[C:14]([C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[CH:13][C:12]([Cl:22])=[CH:11][CH:10]=2)=O)=[O:4].[CH3:23][NH:24][NH2:25]>CO>[CH3:1][O:2][C:3]([C:5]1[N:25]([NH:24][CH3:23])[C:7](=[O:6])[C:9]2[C:14]([C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[CH:13][C:12]([Cl:22])=[CH:11][CH:10]=2)=[O:4]

Participants

4

Reactant 2

HCID 6061MethylhydrazineHCID 691565656-chloro-4-phenylisocoumarin-3-carboxylic Acid Methyl Ester

Product 1

HCID 101259456-chloro-2-methylamino-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl EsterYield 69.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 6-chloro-4-phenylisocoumarin-3-carboxylic acid methyl ester (1.3 g) in methanol (15 ml) was added methylhydrazine (3.0 g) and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated, and the obtained residue was dissolved in methanol (15 ml). Sulfuric acid (1.5 ml) was added and the mixture was refluxed for 2 hrs. The reaction mixture was concentrated, and the residue was neutralized with aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1) and crystallized from isopropyl ether to give the title compound (980 mg) as colorless crystals.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe obtained residue was dissolved in methanol (15 ml)
  3. additionSulfuric acid (1.5 ml) was added
  4. temperaturethe mixture was refluxed for 2 hrs
  5. concentrationThe reaction mixture was concentrated
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with water and brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1)
  11. customcrystallized from isopropyl ether

Sources & evidence

ORD record
ord-941595252bc04a11b72c7d49a9ad390a
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

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