Bisindolylmaleimide V → HCID 18505441, compound

HRID 1357092Notes

Reaction equation

HRID 1357092 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]2[C:11]([N:13]([CH3:26])[C:14](=[O:25])[C:15]=2[C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH:17]=2)=[O:12])=[CH:2]1.Cl.Cl[CH2:29][CH2:30][CH2:31][N:32]([CH3:34])[CH3:33].[H-].[Na+]>CN(C=O)C>[CH3:33][N:32]([CH3:34])[CH2:31][CH2:30][CH2:29][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]2[C:11]([N:13]([CH3:26])[C:14](=[O:25])[C:15]=2[C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH:17]=2)=[O:12])=[CH:2]1

Participants

5

Reactant 3

HCID 2400Bisindolylmaleimide VHCID 24758Sodium hydrideHCID 943083-(Dimethylamino)propyl chloride hydrochloride

Product 1

HCID 18505441HCID 18505441, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (60 to 72%, oily, 50 mg) was washed with pentane and then suspended into DMF (0.3 mL). A DMF solution (1.2 mL) of 2,3-bis(1H-indol-3-yl)-N-methylmaleimide (150 mg, 0.44 mmol) synthesized according to a known method (Tetrahedron, Vol. 44, p. 1887, 1988) was added thereto, and the whole was stirred at room temperature for 45 minutes. On the other hand, DMF (1.2 mL) was added at 0° C. to a mixture of (3-chloropropyl)dimethylamine hydrochloride (70 mg, 0.44 mmol) and sodium hydride (60 to 75%, oily, 18 mg) washed with pentane, and the whole was stirred for 5 minutes and then warmed to room temperature with standing. The supernatant was added to the solution of sodium salt of 2,3-bis(1H-indol-3-yl)-N-methylmaleimide. The resulting mixture was stirred at 40° C. for 1.5 hours, and then DMF was removed under reduced pressure. To the residue were added dichloromethane and saturated aqueous sodium chloride solution, and the organic layer was separated. The water layer was further extracted with dichloromethane. The resulting organic layers were combined and dried over sodium sulfate. The residue obtained by removing the solvent under reduced pressure was purified by column chromatography over silica gel (chloroform saturated with ammonia:methanol=10:1) to obtain 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-N-methylmaleimide (77 mg, 41%) as dark red solids.

Workup

  1. washSodium hydride (60 to 72%, oily, 50 mg) was washed with pentane
  2. additionwas added
  3. washwashed with pentane
  4. stirringthe whole was stirred for 5 minutes
  5. temperaturewarmed to room temperature with standing
  6. additionThe supernatant was added to the solution of sodium salt of 2,3-bis(1H-indol-3-yl)-N-methylmaleimide
  7. stirringThe resulting mixture was stirred at 40° C. for 1.5 hours
  8. customDMF was removed under reduced pressure
  9. additionTo the residue were added dichloromethane and saturated aqueous sodium chloride solution
  10. customthe organic layer was separated
  11. extractionThe water layer was further extracted with dichloromethane
  12. dry with materialdried over sodium sulfate
  13. customThe residue obtained
  14. customby removing the solvent under reduced pressure
  15. customwas purified by column chromatography over silica gel (chloroform saturated with ammonia:methanol=10:1)

Sources & evidence

ORD record
ord-779b19a16fc84bd3b7c968552d1a8e54
Source dataset
uspto-grants-2003_07
Patent number
US06589977B1

Reaction notes

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