Acetic Acid → 1-Benzyl-4-[3-(1-cyano-1-methylethylamino)pyridyl]-piperazine

HRID 1449743Notes

Reaction equation

HRID 1449743 reaction equation
N[C:2]1C=[C:4]2[C:8](=[CH:9][CH:10]=1)N[C:6]([N:11]1[CH2:16][CH2:15][N:14]([C:17]3[C:22]([NH:23]C(C)C)=[CH:21][CH:20]=[CH:19][N:18]=3)[CH2:13][C:12]1=C=O)=[CH:5]2.[CH3:29]C(C)=O.C[Si]([C:37]#[N:38])(C)C.[OH-].[Na+].[C:41](O)(=O)[CH3:42]>CO.C(OCC)(=O)C.CCCCCC>[CH2:6]([N:11]1[CH2:12][CH2:13][N:14]([C:17]2[C:22]([NH:23][C:41]([C:37]#[N:38])([CH3:42])[CH3:29])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:15][CH2:16]1)[C:5]1[CH:2]=[CH:10][CH:9]=[CH:8][CH:4]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 180AcetoneHCID 14798Sodium HydroxideHCID 82115Trimethylsilyl cyanideHCID 867502765-Aminoindolyl-2-carbonyl-4-[3-(1-methylethyl amino)-2-pyridinyl]piperazine

Product 1

HCID 540478341-Benzyl-4-[3-(1-cyano-1-methylethylamino)pyridyl]-piperazine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

The 1-[5-Aminoindolyl -2-carbonyl -4-[3-(1-methylethyl amino)-2-pyridinyl]piperazine (EXAMPLE 7, 11.68 g, 43.51 mmol) is dissolved in 130 ml methanol and 130 ml acetic acid. Acetone (25.6 ml, 348.1 mmol) and trimethylsilylcyanide (46.4 ml, 348.1 mmol) are added and the mixture is stirred twenty hours. The solution is poured into cold aqueous sodium hydroxide solution, stirring vigorously, to give a basic solution. The aqueous solution is then extracted with ethyl acetate, the organic extract is washed with saline, dried over sodium sulfate and evaporated to dryness to give an oily residue of 12.6 g. Chromatography on a 400 g silica gel column with a step gradient of ethyl acetate/hexane (2/3 to 3/2, v/v), pooling and concentrating the appropriate fractions gives the title compound, NMR (300 MHz, CD3OD) 7.65, 7.29-7.17, 6.96-6.92, 3.51, 2.98, 2.55, 1.14 δ.

Workup

  1. stirringstirring vigorously
  2. customto give a basic solution
  3. extractionThe aqueous solution is then extracted with ethyl acetate
  4. extractionthe organic extract
  5. washis washed with saline
  6. dry with materialdried over sodium sulfate
  7. customevaporated to dryness
  8. customto give an oily residue of 12.6 g
  9. concentrationconcentrating the appropriate fractions

Sources & evidence

ORD record
ord-a69ed5980bcc44098a9634312844006e
Source dataset
uspto-grants-1997_02
Patent number
US05599930

Reaction notes

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