Methanol → 6-Fluoro-5-methoxy-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one

HRID 1860991Notes

Reaction equation

HRID 1860991 reaction equation
[F:1][C:2]1[C:3](/[C:12](/I)=[CH:13]/[C:14](=O)[C:15]2[NH:16][CH:17]=[CH:18][CH:19]=2)=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.[H-].[Na+].[CH3:24][OH:25]>>[F:1][C:2]1[C:3]2[C:4]3[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]=3[C:14]([C:15]1[NH:16][CH:17]=[CH:18][CH:19]=1)=[CH:13][C:12]=2[O:25][CH3:24]

Participants

4

Reactant 3

HCID 887MethanolHCID 24758Sodium hydrideHCID 10135347(Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-one

Product 1

HCID 99218236-Fluoro-5-methoxy-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one

Procedure

To a suspension of (Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-one (from Example 8 above) (200 mg, 0.5 mmol) in methanol (20 mL) was added NaH (Aldrich, 60%, 0.6 g, 15 mmol) in portions at room temperature. After stirring at room temperature for 30 minutes, the reaction mixture was heated under reflux for 1.5 hours. The reaction was quenched by pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (20 mL) and extracted with ethyl acetate (3×50 mL). The combined organic extracts were successively washed with water (10 mL) and brine (10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography (silica gel, 25% ethyl acetate in hexanes) to give 6-fluoro-5-methoxy-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one as a yellow solid. (Yield 73.2 mg, 51.9%).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux for 1.5 hours
  3. customThe reaction was quenched
  4. additionby pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (20 mL)
  5. extractionextracted with ethyl acetate (3×50 mL)
  6. washThe combined organic extracts were successively washed with water (10 mL) and brine (10 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by flash chromatography (silica gel, 25% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-2c13e981b36c44f8a5e806a9eb207666
Source dataset
uspto-grants-2003_03
Patent number
US06531598B1

Reaction notes

Loading…