Water → HCID 66836003, compound

HRID 2404462Notes

Reaction equation

HRID 2404462 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([O:23][CH:24]1[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]1)[C:11]1[CH:12]=[C:13]([C:17]#[C:18][CH2:19][CH2:20][CH2:21][NH2:22])[CH:14]=[CH:15][CH:16]=1.O.[OH-].[K+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([O:23][CH:24]1[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]1)[C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][CH2:19][CH2:20][CH2:21][NH2:22])[CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 3

HCID 962WaterHCID 14797Potassium HydroxideHCID 66835900HCID 66835900, compound

Product 1

HCID 66836003HCID 66836003, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 5-{3-[(1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)-methyl]phenyl}pent-4-ynylamine (200 mg) in N,N-dimethylformamide (1.8 mL) are added water (0.05 mL), potassium hydroxide (42 mg) and palladium(II) acetate. The tube is evacuated, filled with argon and sealed. After stirring at 120° C. for 24 h, the mixture is filtered on celite, and the solvent removed under reduced pressure diluted with water and the aqueous phase is extracted with ethyl acetate. The pooled organic extracts are washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography (gradient dichloromethane/methanol/ammonia from 90/10/0 to 90/10/1) to give 5-{3-[(1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]phenyl}pent-4-enylamine.

Workup

  1. customThe tube is evacuated
  2. additionfilled with argon
  3. customsealed
  4. filtrationthe mixture is filtered on celite
  5. customthe solvent removed under reduced pressure
  6. additiondiluted with water
  7. extractionthe aqueous phase is extracted with ethyl acetate
  8. washThe pooled organic extracts are washed with water
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue is purified by chromatography (gradient dichloromethane/methanol/ammonia from 90/10/0 to 90/10/1)

Sources & evidence

ORD record
ord-895b559d52c64180bbe9fc152a739db0
Source dataset
uspto-grants-2014_08
Patent number
US08802664B2

Reaction notes

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