Sodium hydride → HCID 59552312, compound

HRID 1861008Notes

Reaction equation

HRID 1861008 reaction equation
F[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+]>CN(C=O)C.C(OCC)(=O)C.O>[NH:16]1[CH:17]=[CH:18][CH:19]=[C:15]1[C:14]1[C:5]2[C:6](=[O:11])[NH:7][C:8]3=[CH:9][CH:10]=[CH:2][C:3]([C:4]=23)=[CH:12][CH:13]=1

Participants

6

Reactant 2

HCID 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 59552312HCID 59552312, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture 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) (250 mg, 0.504 mmol) and 3-R-hydroxy pyrrolidine (Aldrich, 870 mg, 9.99 mmol) in DMF (5 mL) was treated with NaH (Aldrich, 120 mg, 5.04 mmol). The mixture was stirred at approximately 110° C. for 2.5 hours and then at room temperature overnight. The reaction mixture was poured in a mixture of ethyl acetate and water. The aqueous layer was extracted a few more times with ethyl acetate and the combined organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography (silica gel, with 0-100% ethyl acetate in hexanes and then 0-100% THF in ethyl acetate) to give 6-fluoro-5-[(R)-3-hydroxy-pyrrolidin-1-yl)]-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one as a yellow-green solid. (Yield 6 mg, 5%).

Workup

  1. customat room temperature
  2. customovernight
  3. extractionThe aqueous layer was extracted a few more times with ethyl acetate
  4. dry with materialthe combined organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (silica gel

Sources & evidence

ORD record
ord-796f05d3792449a887f4c459fb78e113
Source dataset
uspto-grants-2003_03
Patent number
US06531598B1

Reaction notes

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