Dimethylformamide → 6-chloro-3-(1-(2-(1-methylpyrazol-4-yl)ethyl)piperidin-4-yl)-1H-indole

HRID 1003573Notes

Reaction equation

HRID 1003573 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:23][N:24]([CH3:27])C=O>>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]3[CH2:16][CH2:15][N:14]([CH2:4][CH2:5][C:6]4[CH:7]=[N:8][N:24]([CH3:27])[CH:23]=4)[CH2:13][CH2:12]3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 10340Sodium CarbonateHCID 120720406-Chloro-3-piperidin-4-YL-1H-indole

Product 1

HCID 187974106-chloro-3-(1-(2-(1-methylpyrazol-4-yl)ethyl)piperidin-4-yl)-1H-indoleYield 59.8%

Procedure

To a mixture of 2.0 gm (8.5 mMol) 6-chloro-3-(piperidin-4-yl)-1H-indole and 2.25 gm (21 mMol) sodium carbonate in 20 mL dimethylformamide was added a solution of 1.74 gm (8.4 mMol) 1-methyl-4-(2-methanesulfonyloxy)ethyl-1H-pyrazole in a minimal volume of dimethylformamide. The resultant mixture was heated at 100° C. for 18 hours. The reaction mixture was then cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between dichloromethane and water. The organic phase was separated and washed first with water and then with saturated aqueous sodium chloride. The remaining organics were dried over sodium sulfate and concentrated under reduced pressure to give a yellow oil. This residue was subjected to silica gel chromatography, eluting with dichloromethane containing 5% methanol. Fractions shown to contain product were combined and concentrated under reduced pressure to give 1.74 gm (59.8%) of 6-chloro-3-(1-(2-(1-methylpyrazol-4-yl)ethyl)piperidin-4-yl)-1H-indole as a yellow foam. The oxalate salt was formed and crystallized from methanol to provide the title compound as yellow crystals.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was partitioned between dichloromethane and water
  3. customThe organic phase was separated
  4. washwashed first with water
  5. dry with materialThe remaining organics were dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give a yellow oil
  8. washeluting with dichloromethane containing 5% methanol
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7aeaae17b9c74539bd3aad998014860b
Source dataset
uspto-grants-2000_04
Patent number
US06046215

Reaction notes

Loading…