Sodium hydride → HCID 23550272, compound

HRID 1861014Notes

Reaction equation

HRID 1861014 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.[C:22]([O:26][C:27](=[O:32])[NH:28][CH2:29][CH2:30][SH:31])([CH3:25])([CH3:24])[CH3:23].[H-].[Na+].[H][H]>>[C:22]([O:26][C:27](=[O:32])[NH:28][CH2:29][CH2:30][S:31][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)([CH3:25])([CH3:23])[CH3:24]

Participants

5

Reactant 4

HCID 24758Sodium hydrideHCID 3017761N-(tert-butoxycarbonyl)-2-aminoethanethiolHCID 10135347(Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-oneHCID 178418361HCID 178418361, compound

Product 1

HCID 23550272HCID 23550272, compound

Conditions

Temperature
120 °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) (600 mg, 1.28 mmol) and neat tert-butyl-N-(2-mercaptoethyl)-carbamate (Aldrich, 19 mL) was treated with NaH (Aldrich, 460 mg, 19.15 mmol) in small portions e within a period of 30 minutes at room temperature. After the evolution of hydrogen had stopped, the mixture was heated gradually to 120° C. The viscous slurry was stirred at this temperature for 2 hours and then allowed to cool. The mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted twice more with ethyl acetate. The combined organic layer was dried and concentrated to give a solid residue. This residue was washed with pentane and purified by HPLC (silica gel, 25% ethyl acetate in hexanes), followed by precipitation out of THF with excess pentane to give [2-[6-fluoro-2-oxo-3-(1H-pyrrol-2-yl)-1,2-dihydro-benzo[cd]indol-5-ylsulfanyl]-ethyl]-carbamic acid tert-butyl ester as a yellow solid. (Yield 470 mg, 84%).

Workup

  1. temperatureto cool
  2. customThe mixture was partitioned between ethyl acetate and water
  3. extractionThe aqueous layer was extracted twice more with ethyl acetate
  4. customThe combined organic layer was dried
  5. concentrationconcentrated
  6. customto give a solid residue
  7. washThis residue was washed with pentane
  8. custompurified by HPLC (silica gel, 25% ethyl acetate in hexanes)
  9. customfollowed by precipitation out of THF with excess pentane

Sources & evidence

ORD record
ord-71edbd4a40a14663b6099fa36465f7a3
Source dataset
uspto-grants-2003_03
Patent number
US06531598B1

Reaction notes

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