(+/-)-Ethyl (4-amino-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl)acetate → 2a-Methyl-2a,5-dihydropyrrolo[4,3,2-de]quinoline-2,4(1H,3H)-dione

HRID 2426155Notes

Reaction equation

HRID 2426155 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH2:13][C:14]([O:16]CC)=O)([CH3:12])[C:5](=[O:11])[NH:6]2>CC(O)=O>[CH3:12][C:4]12[C:5](=[O:11])[NH:6][C:7]3[C:3]1=[C:2]([CH:10]=[CH:9][CH:8]=3)[NH:1][C:14](=[O:16])[CH2:13]2

Participants

3

Reactant 1

HCID 86629727(+/-)-Ethyl (4-amino-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl)acetate

Product 1

HCID 576637492a-Methyl-2a,5-dihydropyrrolo[4,3,2-de]quinoline-2,4(1H,3H)-dione

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of (±)-ethyl (4-amino-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl)acetate from Step C (2.37 g, 9.56 mmol) and AcOH (1 mL) was heated in xylenes (10 mL) at reflux for 24 h, then concentrated to dryness under reduced pressure. The crude product was partially purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH:NH4H—100:0:0 to 90:9:1, to give a crude sample of the title compound. Further purification by silica gel chromatography, eluting with a gradient of CH2Cl2:EtOAc—100:0 to 0:100, gave the racemic title compound. The enantiomers were resolved by HPLC, utilizing a ChiralPak AS column and eluting with hexane:EtOH—70:30. The first major peak to elute was 2a-methyl-2a,5-dihydropyrrolo[4,3,2-de]quinoline-2,4(1H,3H)-dione, enantiomer A, and the second major peak to elute was 2a-methyl-2a,5-dihydropyrrolo[4,3,2-de]quinoline-2,4(1H,3H)-dione, enantiomer B, the title compound. MS: m/z=203 (M+1).

Workup

  1. temperatureat reflux for 24 h
  2. concentrationconcentrated to dryness under reduced pressure
  3. customThe crude product was partially purified by silica gel chromatography
  4. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-26541ec515234e7aaba10620ede765f6
Source dataset
uspto-grants-2011_06
Patent number
US07968540B2

Reaction notes

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