5-fluoro-3-(piperidin-4-yl)-1H-indole → 5-fluoro-3-[1-(2-(4-pyridinyl)acetyl)-4-piperidinyl]-1H-indole

HRID 440925Notes

Reaction equation

HRID 440925 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.[N:17]1[CH:22]=[CH:21][C:20]([CH2:23][C:24](OOC2C(Cl)=CC(Cl)=C(Cl)C=2)=[O:25])=[CH:19][CH:18]=1>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:16][CH2:15][N:14]([C:24](=[O:25])[CH2:23][C:20]2[CH:21]=[CH:22][N:17]=[CH:18][CH:19]=2)[CH2:13][CH2:12]1

Participants

4

Reactant 2

HCID 117699295-fluoro-3-(piperidin-4-yl)-1H-indoleHCID 196965283,4,6-Trichlorophenoxy 2-(4-pyridinyl)acetate

Product 1

HCID 196965245-fluoro-3-[1-(2-(4-pyridinyl)acetyl)-4-piperidinyl]-1H-indole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1.0 gm (3.73 mMol) 5-fluoro-3-(4-piperidinyl)-1H-indole and 2.4 gm (7.5 mMol) 3,4,6-trichlorophenoxy 2-(4-pyridinyl)acetate in 40 mL dimethylformamide were stirred at ambient temperature for 18 hours under a nitrogen atmosphere. The reaction mixture was concentrated under reduced pressure and the residue partitioned between ethyl acetate and aqueous sodium bicarbonate solution. The phases were separated and the organic extract dried over sodium sulfate then concentrated under reduced pressure. The resultant oil was subjected to silica gel chromatography, eluting with a gradient of ethyl acetate containing 0-5% methanol. Fractions shown to contain the desired amide were combined and concentrated under reduced pressure to give 5-fluoro-3-[1-(2-(4-pyridinyl)acetyl)-4-piperidinyl]-1H-indole as a colorless solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue partitioned between ethyl acetate and aqueous sodium bicarbonate solution
  3. customThe phases were separated
  4. extractionthe organic extract
  5. dry with materialdried over sodium sulfate
  6. concentrationthen concentrated under reduced pressure
  7. washeluting with a gradient of ethyl acetate containing 0-5% methanol
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f44687d66ac94d4984cc8fa527085883
Source dataset
uspto-grants-1996_05
Patent number
US05521196

Reaction notes

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