Methylamine → N-methyl-1-(1-benzyloxycarbonylpiperidin-4-yl)-1H-indole-6-carboxamide

HRID 494914Notes

Reaction equation

HRID 494914 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]([OH:28])=O)[CH:24]=3)[CH:19]=[CH:18]2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:29](N1C=CN=C1)([N:31]1C=CN=C1)=O.CN>O1CCCC1>[CH3:29][NH:31][C:26]([C:23]1[CH:24]=[C:25]2[C:20]([CH:19]=[CH:18][N:17]2[CH:14]2[CH2:13][CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[O:10])[CH2:16][CH2:15]2)=[CH:21][CH:22]=1)=[O:28]

Participants

5

Reactant 3

HCID 6329MethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 576829061-(1-benzyloxycarbonylpiperidin-4-yl)-1H-indole-6-carboxylic acid

Product 1

HCID 57682860N-methyl-1-(1-benzyloxycarbonylpiperidin-4-yl)-1H-indole-6-carboxamideYield 85.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2.00 g of 1-(1-benzyloxycarbonylpiperidin-4-yl)-1H-indole-6-carboxylic acid was dissolved in 20 ml of tetrahydrofuran, and 1.03 g of 1,1′-carbonylbis-1H-imidazole was then added thereto. The obtained mixture was stirred at room temperature for 1.5 hours, and 4.11 ml of a 40% methylamine aqueous solution was added thereto. After completion of the reaction, the reaction solution was extracted with ethyl acetate. The organic layer was washed with a saturated sodium bicarbonate aqueous solution, a saturated ammonium chloride aqueous solution, and a saturated sodium chloride solution. Thereafter, the organic layer was dried over anhydrous magnesium sulfate. After removing the drying agent by filtration, the organic layer was concentrated under a reduced pressure, and the residue was then purified by NH silica gel column chromatography (ethyl acetate) and silica gel column chromatography (hexane/ethyl acetate), so as to obtain 1.77 g of the subject compound.

Workup

  1. customAfter completion of the reaction
  2. extractionthe reaction solution was extracted with ethyl acetate
  3. washThe organic layer was washed with a saturated sodium bicarbonate aqueous solution
  4. dry with materialThereafter, the organic layer was dried over anhydrous magnesium sulfate
  5. customAfter removing the drying agent
  6. filtrationby filtration
  7. concentrationthe organic layer was concentrated under a reduced pressure
  8. customthe residue was then purified by NH silica gel column chromatography (ethyl acetate) and silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-aa5b158d46d746b680ebfd50bfdfa376
Source dataset
uspto-grants-2009_05
Patent number
US07538123B2

Reaction notes

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