(Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-one → HCID 9921498, compound

HRID 1861002Notes

Reaction equation

HRID 1861002 reaction equation
[CH3:1][Li].[F:3][C:4]1[C:5](/[C:14](/I)=[CH:15]/[C:16](=O)[C:17]2[NH:18][CH:19]=[CH:20][CH:21]=2)=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:13])[CH2:7]2>C1COCC1.[Cu]I>[F:3][C:4]1[C:5]2[C:6]3[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:13])[C:7]=3[C:16]([C:17]1[NH:18][CH:19]=[CH:20][CH:21]=1)=[CH:15][C:14]=2[CH3:1]

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 178418348HCID 178418348, compound

Product 1

HCID 9921498HCID 9921498, 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 methyllithium (Aldrich, 1.4 M solution in ether, 1.42 mL, 2.0 mmol), under argon, at 0° C. and the reaction mixture was stirred for 15 minutes. To the colorless 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 another 45 minutes, the reaction mixture was 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 (28.5 mg) which was further purified by preparative TLC (silica gel, 20% ethyl acetate in hexanes) to afford 6-fluoro-5-methyl-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one as a yellow solid. (Yield 12.6 mg, 47.4%).

Workup

  1. customTo the colorless solution obtained
  2. stirringAfter stirring at 0° C. for another 45 minutes
  3. customthe reaction mixture was quenched with a saturated aqueous ammonium chloride solution (10 mL)
  4. extractionextracted with ethyl acetate (3×20 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. customto give crude product (28.5 mg) which
  10. customwas further purified by preparative TLC (silica gel, 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-148f72c3a8d24643ac856470d44fc39d
Source dataset
uspto-grants-2003_03
Patent number
US06531598B1

Reaction notes

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