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

HRID 1860993Notes

Reaction equation

HRID 1860993 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]([CH2:24][NH2:25])[OH:23].[H-].[Na+]>CN(C=O)C>[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[NH:25][CH2:24][CH2:22][OH:23]

Participants

5

Reactant 3

HCID 700EthanolamineHCID 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 99445486-Fluoro-5-(2-hydroxy-ethylamino)-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To a solution 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) (396 mg, 1.0 mmol) in DMF (4.0 mL) and ethanolamine (Aldrich, 0.6 mL, 610 mg, 10.0 mmol) was added NaH (Aldrich, 95%, 270 mg, 10.0 mmol) in portions at 0° C. After stirring at the same temperature for 10 minutes, the reaction mixture was heated to 130° C. for 2 hours. The reaction was quenched by pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (30 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, 20% ethyl acetate in hexanes) to afford 6-fluoro-5-(2-hydroxy-ethylamino)-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one as a yellow solid. (Yield 25.0 mg, 8.0%).

Workup

  1. customThe reaction was quenched
  2. additionby pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (30 mL)
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. washThe combined organic extracts were successively washed with water (20 mL) and brine (20 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography (silica gel, 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-d1262001ff544668a20563ce26b941d0
Source dataset
uspto-grants-2003_03
Patent number
US06531598B1

Reaction notes

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