Potassium Hydroxide → 3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-5-carbonitrile

HRID 1003555

Reaction equation

HRID 1003555 reaction equation
[OH-].[K+].[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[CH:8]2)#[N:4].O.Cl.[NH:16]1[CH2:21][CH2:20][C:19](=O)[CH2:18][CH2:17]1>CO>[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[C:8]2[C:19]1[CH2:20][CH2:21][NH:16][CH2:17][CH:18]=1)#[N:4]

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 27513Indole-5-carbonitrileHCID 2723901Piperonylamine

Product 1

HCID 113335543-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-5-carbonitrileYield 60%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 8.8 gm (157 mMol) potassium hydroxide in 85 mL methanol were added 8.15 gm (57.33 mMol) 5-cyano-1H-indole and 7.86 gm (51.17 mMol) 4-piperidone hydrochloride monohydrate. The resulting mixture was heated to reflux for 48 hours and was then allowed to cool to room temperature. The reaction mixture was concentrated under reduced pressure to about half volume and was then treated with 1M HCl until the pH of the solution was between 1 and 2. The resulting solution was extracted twice with 100 mL of diethyl ether and the remaining aqueous phase was treated with 5N sodium hydroxide until the pH of the solution was between 12 and 14. This aqueous phase was extracted 5 times with 10% methanol in dichloromethane. These organic phases were combined, dried over sodium sulfate and concentrated under reduced pressure to a residue. This residue was subjected to flash silica gel chromatography, eluting with dichloromethane which contained 20% methanol and 2% ammonium hydroxide. Fractions shown to contain product were combined and concentrated under reduced pressure to give 6.86 gm (60%) of the title compound as a solid.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 48 hours
  3. concentrationThe reaction mixture was concentrated under reduced pressure to about half volume
  4. additionwas then treated with 1M HCl until the pH of the solution
  5. extractionThe resulting solution was extracted twice with 100 mL of diethyl ether
  6. additionthe remaining aqueous phase was treated with 5N sodium hydroxide until the pH of the solution
  7. extractionThis aqueous phase was extracted 5 times with 10% methanol in dichloromethane
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under reduced pressure to a residue
  10. washeluting with dichloromethane which
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-af4ada88085d48588c6b374106a1c65f
Source dataset
uspto-grants-2000_04
Patent number
US06046215

Linked notes

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