Lithium Chloride → HCID 9965506, compound

HRID 1633779Notes

Reaction equation

HRID 1633779 reaction equation
[Cu]C#N.[Cl-].[Li+].[CH2:6]([Zn]CC)[CH3:7].[F:11][C:12]1[C:13](/[C:22](/I)=[CH:23]/[C:24](=O)[C:25]2[NH:26][CH:27]=[CH:28][CH:29]=2)=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16](=[O:21])[CH2:15]2>C1COCC1>[CH2:6]([C:22]1[CH:23]=[C:24]([C:25]2[NH:26][CH:27]=[CH:28][CH:29]=2)[C:15]2[C:16](=[O:21])[NH:17][C:18]3[C:14]=2[C:13]=1[C:12]([F:11])=[CH:20][CH:19]=3)[CH3:7]

Participants

6

Reactant 4

HCID 433294Lithium ChlorideHCID 10135347(Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-oneHCID 178418546HCID 178418546, compoundHCID 178418750HCID 178418750, compound

Product 1

HCID 9965506HCID 9965506, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a suspension of copper(I) cyanide (Aldrich, 27 mg, 0.3 mmol) and lithium chloride (Fluka, 25.5 mg, 0.6 mmol) in dry THF (2 mL) was added diethylzinc (Aldrich, 1.0 M solution in n-hexane, 3.0 mL, 3.0 mmol), under argon, at −20° C. and the reaction mixture was stirred for 30 minutes at the same temperature. The light green reaction mixture was then cooled to −78° C. and treated dropwise with 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) (79.2 mg, 0.2 mmol) in dry THF (4 mL). After stirring at the same temperature for 1 hour, the reaction mixture was allowed to warm up slowly to room temperature overnight, then heated under reflux for 3 hours. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution (20 mL) and extracted with ethyl acetate (3×30 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 to give crude product which was further purified by preparative TLC (silica gel, 20% ethyl acetate in hexanes) to afford 5-ethyl-6-fluoro-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one as a yellow solid. (Yield 10.6 mg, 18.9%).

Workup

  1. temperatureThe light green reaction mixture was then cooled to −78° C.
  2. stirringAfter stirring at the same temperature for 1 hour
  3. temperatureto warm up slowly to room temperature overnight
  4. temperatureheated
  5. temperatureunder reflux for 3 hours
  6. customThe reaction mixture was quenched with a saturated aqueous ammonium chloride solution (20 mL)
  7. extractionextracted with ethyl acetate (3×30 mL)
  8. washThe combined organic extracts were successively washed with water (20 mL) and brine (20 mL)
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto give crude product which
  13. customwas further purified by preparative TLC (silica gel, 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-7afda0e4927742909b98950e80f4e707
Source dataset
uspto-grants-2003_01
Patent number
US06504034B2

Reaction notes

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