Sodium amide → 1-[3-Cyano-3,3-bis-(2-pyridyl)propyl]-4-(2-methoxyphenyl)piperazine

HRID 2181635Notes

Reaction equation

HRID 2181635 reaction equation
[NH2-].[Na+].[N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1)[C:10]#[N:11].Cl[CH2:19][CH2:20][N:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[O:33][CH3:34])[CH2:23][CH2:22]1>COCCOC.O>[C:10]([C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1)([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][N:3]=1)[CH2:19][CH2:20][N:21]1[CH2:22][CH2:23][N:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[O:33][CH3:34])[CH2:25][CH2:26]1)#[N:11]

Participants

6

Reactant 3

HCID 24533Sodium amideHCID 5956731-(2-Chloroethyl)-4-(2-methoxyphenyl)piperazineHCID 140060572,2-Bis-(2-pyridyl)acetonitrile

Product 1

HCID 224821111-[3-Cyano-3,3-bis-(2-pyridyl)propyl]-4-(2-methoxyphenyl)piperazineYield 68.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent3×

Procedure

To a suspension of 0.21 g of 95% sodium amide in 2 mL of 1,2-dimethoxyethane was added dropwise a solution of 0.78 g of 2,2-bis-(2-pyridyl)acetonitrile (prepared as described in Heterocycles 1995, 40, 757) in 8 mL of 1,2-dimethoxyethane, with stirring under a nitrogen atmosphere at room temperature. After 1 h, there were added dropwise, 1.02 g of 1-(2-chloroethyl)-4-(2-methoxy-phenyl)piperazine dissolved in 4 mL of 1,2-dimethoxyethane. The resultant reaction mixture was then refluxed for 20 h, followed by cooling to room temperature, and was then poured cautiously into 40 g of ice, diluted with water, and extracted with ethyl acetate. The combined organic phases were then washed with water, dried on sodium sulphate, and then evaporated thoroughly under vacuum. The obtained crude was then purified by flash chromatography (ethyl acetate-methanol gradient from 10:0 to 9:1). The recovered fractions were then evaporated to complete dryness, affording 1.13 g of the title product (68.4%).

Workup

  1. additionthere were added dropwise
  2. customThe resultant reaction mixture
  3. temperaturewas then refluxed for 20 h
  4. temperatureby cooling to room temperature
  5. extractionextracted with ethyl acetate
  6. washThe combined organic phases were then washed with water
  7. customdried on sodium sulphate
  8. customevaporated thoroughly under vacuum
  9. customThe obtained crude
  10. customwas then purified by flash chromatography (ethyl acetate-methanol gradient from 10:0 to 9:1)
  11. customThe recovered fractions were then evaporated

Sources & evidence

ORD record
ord-73501f0331dd48a8939dfbf41a4012d4
Source dataset
uspto-grants-2005_05
Patent number
US06894052B1

Reaction notes

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