Sodium hydride → [2-[6-fluoro-2-oxo-3-(1H-pyrrol-2-yl)-1,2-dihydro-benzo[cd]indol-5-yloxy]-ethyl]-carbamic acid tert-butyl ester

HRID 1633771Notes

Reaction equation

HRID 1633771 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.[OH:22][CH2:23][CH2:24][NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29].[H-].[Na+]>>[C:28]([O:27][C:26](=[O:32])[NH:25][CH2:24][CH2:23][O:22][C:12]1[CH:13]=[C:14]([C:15]2[NH:16][CH:17]=[CH:18][CH:19]=2)[C:5]2[C:6](=[O:11])[NH:7][C:8]3[C:4]=2[C:3]=1[C:2]([F:1])=[CH:10][CH:9]=3)([CH3:31])([CH3:29])[CH3:30]

Participants

4

Reactant 3

HCID 24758Sodium hydrideHCID 2733206tert-butyl N-(2-hydroxyethyl)carbamateHCID 10135347(Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-one

Product 1

HCID 23550271[2-[6-fluoro-2-oxo-3-(1H-pyrrol-2-yl)-1,2-dihydro-benzo[cd]indol-5-yloxy]-ethyl]-carbamic acid tert-butyl ester

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) (79.2 mg, 0.2 mmol) in tert-butyl N-(2-hydroxyethyl)-carbamate (Aldrich, 3 mL, 18.9 mmol) was added NaH (Aldrich, 60%, 0.2 g, 5.0 mmol) in portions at room temperature. After stirring at room temperature for 30 minutes, the reaction mixture was heated to 120° C. for 3.0 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 (3×30 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, 50% ethyl acetate in hexanes) to give [2-[6-fluoro-2-oxo-3-(1H-pyrrol-2-yl)-1,2-dihydro-benzo[cd]indol-5-yloxy]-ethyl]-carbamic acid tert-butyl ester as a yellow solid. (Yield 17.7 mg, 21.5%).

Workup

  1. temperaturethe reaction mixture was heated to 120° C. for 3.0 hours
  2. customThe reaction was quenched
  3. additionby pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (20 mL)
  4. extractionextracted with ethyl acetate (3×30 mL)
  5. washThe combined organic extracts were successively washed with water (10 mL) and brine (10 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-2d8e5b6b3ccf487782d091bcb891d83a
Source dataset
uspto-grants-2003_01
Patent number
US06504034B2

Reaction notes

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