(Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-one → HCID 9944451, compound

HRID 1861003Notes

Reaction equation

HRID 1861003 reaction equation
[CH:1]([Li])([CH2:3][CH3:4])[CH3:2].[F:6][C:7]1[C:8](/[C:17](/I)=[CH:18]/[C:19](=O)[C:20]2[NH:21][CH:22]=[CH:23][CH:24]=2)=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][C:11](=[O:16])[CH2:10]2>C1COCC1.[Cu]I>[CH:1]([C:17]1[CH:18]=[C:19]([C:20]2[NH:21][CH:22]=[CH:23][CH:24]=2)[C:10]2[C:11](=[O:16])[NH:12][C:13]3[C:9]=2[C:8]=1[C:7]([F:6])=[CH:15][CH:14]=3)([CH2:3][CH3:4])[CH3:2]

Participants

5

Reactant 2

HCID 10135347(Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-oneHCID 178418400CID 53628100

Product 1

HCID 9944451HCID 9944451, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of copper(I) iodide (Aldrich, 190 mg, 1.0 mmol) in dry THF (2 mL) was added sec-butyllithium (Aldrich, 1.3 M solution in ether, 1.53 mL, 2.0 mmol), under argon, at 0° C. and the reaction mixture was stirred for 30 minutes. To the resulting brown solution obtained was added dropwise 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) (39.6 mg, 0.1 mmol) in THF (2 mL). After stirring at 0° C. for 45 minutes, the reaction mixture was stirred at room temperature for another 2 hours, then quenched with a saturated aqueous ammonium chloride solution (10 mL) and extracted with ethyl acetate (3×20 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 to give crude product which was further purified by preparative TLC (silica gel, 20% ethyl acetate in hexanes) to afford (rac)-5-sec-butyl-6-fluoro-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one as a yellow solid. (Yield 3.6 mg, 11.7%).

Workup

  1. customTo the resulting brown solution obtained
  2. stirringAfter stirring at 0° C. for 45 minutes
  3. stirringthe reaction mixture was stirred at room temperature for another 2 hours
  4. customquenched with a saturated aqueous ammonium chloride solution (10 mL)
  5. extractionextracted with ethyl acetate (3×20 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. customto give crude product which
  11. customwas further purified by preparative TLC (silica gel, 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5403b892a9f64393a995b7b6587ffd2d
Source dataset
uspto-grants-2003_03
Patent number
US06531598B1

Reaction notes

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