Sodium Hydroxide → HCID 66650477, compound

HRID 418554Notes

Reaction equation

HRID 418554 reaction equation
[OH-:1].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([N:16]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33]#[N:34])[CH:28]=2)[C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=2)[NH:22][CH:21]=[CH:20]3)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>O.CCO>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([N:16]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33](=[O:1])[NH2:34])[CH:28]=2)[C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=2)[NH:22][CH:21]=[CH:20]3)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 66650370HCID 66650370, compound

Product 1

HCID 66650477HCID 66650477, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A solution of NaOH (54 mg, 1.35 mmol) in water (0.2 mL) was added to a solution of 4-[(3-cyano-benzyl)-(1H-indol-5-yl)-amino]-piperidine-1-carboxylic acid tert-butyl ester (115 mg, 0.27 mmol) (prepared as described in Example 2 Step 1) in EtOH (10 mL). The reaction mixture was heated at reflux for 16 hours, the solvent was evaporated and the residue was purified by flash chromatography (0% to 25% of MeOH in DCM) to give 4-[(3-carbamoyl-benzyl)-(1H-indol-5-yl)-amino]-piperidine-1-carboxylic acid tert-butyl ester. This material was dissolved in DCM (5 mL) and trifluoroacetic acid (1 mL) was added. The reaction mixture was stirred for 16 hours, it was then evaporated under reduced pressure and the residue was basified by addition of an aqueous solution of NH4OH. The crude material was purified first by flash chromatography and then by preparative HPLC (Agilent Technologies Zorbax SB-Phenyl column (21.2 mm inner diameter by 100 mm length, 7 micron particle size), water (0.1% TFA added)/acetonitrile 75/25 gradient to 5/95 over 10 minutes at 20 ml/min flow rate) to give the desired 3-{[(1H-indol-5-yl)-piperidin-4-yl-amino]-methyl}-benzamide trifluoroacetate, MS=349 [M+H]+.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 16 hours
  3. customthe solvent was evaporated
  4. customthe residue was purified by flash chromatography (0% to 25% of MeOH in DCM)

Sources & evidence

ORD record
ord-89ffa27662a54be880b4738ea1c84aa9
Source dataset
uspto-grants-2012_01
Patent number
US08093285B2

Reaction notes

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