1,3-Propanediol → 6-Fluoro-5-(3-hydroxy-propoxy)-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one

HRID 1860995Notes

Reaction equation

HRID 1860995 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.[CH2:22]([OH:26])[CH2:23][CH2:24][OH:25].[H-].[Na+]>>[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][CH2:24][CH2:23][CH2:22][OH:26]

Participants

4

Reactant 3

HCID 104421,3-PropanediolHCID 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 98585056-Fluoro-5-(3-hydroxy-propoxy)-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) (198 mg, 0.5 mmol) in 1,3-propanediol (Fluka, 7.0 g, 92 mmol) was added NaH (Aldrich, 60%, 0.5 g, 12.5 mmol) in portions at room temperature. After stirring at room temperature for 30 minutes, the reaction mixture was heated to 110° C. for 2.5 hours. The reaction was quenched by pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic extracts were successively washed with water (20 mL) and brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography (silica gel, 50% ethyl acetate in hexanes) to afford 6-fluoro-5-(3-hydroxy-propoxy)-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one as a yellow solid. (Yield 51.5 mg, 31.6%).

Workup

  1. temperaturethe reaction mixture was heated to 110° C. for 2.5 hours
  2. customThe reaction was quenched
  3. additionby pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (50 mL)
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. washThe combined organic extracts were successively washed with water (20 mL) and brine (20 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography (silica gel, 50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5a5186c410894fa5aaf29afd43b6efa8
Source dataset
uspto-grants-2003_03
Patent number
US06531598B1

Reaction notes

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