Dimethylformamide → N1-Cyclopropyl-5-[(2-{[4-(4-hydroxypiperidino)butanoyl]amino}-4-pyridyl)oxy]-1H-1-indolecarboxamide

HRID 387806Notes

Reaction equation

HRID 387806 reaction equation
[CH:1]1([NH:4][C:5](=O)[O:6]C2C=CC=CC=2)[CH2:3][CH2:2]1.[OH:14][CH:15]1[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][CH2:23][C:24]([NH:26][C:27]2[CH:32]=[C:31]([O:33][C:34]3[CH:35]=[C:36]4[C:40](=[CH:41][CH:42]=3)[NH:39][CH:38]=[CH:37]4)[CH:30]=[CH:29][N:28]=2)=[O:25])[CH2:17][CH2:16]1.[H-].[Na+].CN(C)C=O>O>[CH:1]1([NH:4][C:5]([N:39]2[C:40]3[C:36](=[CH:35][C:34]([O:33][C:31]4[CH:30]=[CH:29][N:28]=[C:27]([NH:26][C:24](=[O:25])[CH2:23][CH2:22][CH2:21][N:18]5[CH2:17][CH2:16][CH:15]([OH:14])[CH2:20][CH2:19]5)[CH:32]=4)=[CH:42][CH:41]=3)[CH:37]=[CH:38]2)=[O:6])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 13648483Phenyl cyclopropylcarbamateHCID 672022485-[(2-{[4-(4-Hydroxypiperidino)butanoyl]amino}-4-pyridyl)oxy]indole

Product 1

HCID 58931039N1-Cyclopropyl-5-[(2-{[4-(4-hydroxypiperidino)butanoyl]amino}-4-pyridyl)oxy]-1H-1-indolecarboxamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Phenyl N-cyclopropylcarbamate (120 mg) was added to a solution of 260 mg of 5-[(2-{[4-(4-hydroxypiperidino)butanoyl]amino}-4-pyridyl)oxy]indole, 53 mg of sodium hydride (60% in oil) and 5 ml of dimethylformamide while stirring at room temperature. After stirring for 10 minutes, water was added and extraction was performed with ethyl acetate. NH type silica gel was added to the ethyl acetate layer, the solvent was distilled off under reduced pressure and the reaction product was adsorbed onto the silica gel. The silica gel was charged into a dry column packed with NH type silica gel, and purification was performed by column chromatography (chloroform:methanol=30:1). The solvent was distilled off under reduced pressure, and the residue was dissolved in ethyl acetate and washed twice with 1N aqueous sodium hydroxide. After drying over sodium sulfate, the solvent was distilled off under reduced pressure to obtain 20 mg of the target substance as a white powder.

Workup

  1. stirringAfter stirring for 10 minutes
  2. extractionextraction
  3. additionNH type silica gel was added to the ethyl acetate layer
  4. distillationthe solvent was distilled off under reduced pressure
  5. additionThe silica gel was charged into a dry column
  6. custompacked with NH type silica gel, and purification
  7. distillationThe solvent was distilled off under reduced pressure
  8. dissolutionthe residue was dissolved in ethyl acetate
  9. washwashed twice with 1N aqueous sodium hydroxide
  10. dry with materialAfter drying over sodium sulfate
  11. distillationthe solvent was distilled off under reduced pressure
  12. customto obtain 20 mg of the target substance as a white powder

Sources & evidence

ORD record
ord-7f04e5bb905548d5a8d269bc417c68b4
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

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