1,4-Dibromobutane → 1-[1,1-Dimethylethoxycarbonyl]-4-[3-(1-pyrrolidinyl)-2-pyridinyl]piperazine

HRID 864404Notes

Reaction equation

HRID 864404 reaction equation
[CH3:1][C:2]([CH3:20])([O:4][C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13]2[C:18]([NH2:19])=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:9][CH2:8]1)=[O:6])[CH3:3].Br[CH2:22][CH2:23][CH2:24][CH2:25]Br.C(=O)([O-])[O-].[K+].[K+].BrC(C(Br)C)C>C(#N)C.O>[CH3:3][C:2]([CH3:20])([O:4][C:5]([N:7]1[CH2:8][CH2:9][N:10]([C:13]2[C:18]([N:19]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:11][CH2:12]1)=[O:6])[CH3:1]

Participants

7

Reactant 4

HCID 80561,4-DibromobutaneHCID 11430Potassium CarbonateHCID 215082,3-DibromobutaneHCID 2756375tert-Butyl 4-(3-aminopyridin-2-yl)piperazine-1-carboxylate

Product 1

HCID 214776341-[1,1-Dimethylethoxycarbonyl]-4-[3-(1-pyrrolidinyl)-2-pyridinyl]piperazine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

1-[1,1-Dimethylethoxycarbonyl]-4-[3-amino-2-pyridinyl]piperazine (International Publication No. WO 88/08424, 0.50 g), 1,4-dibromobutane (0.21 ml) and potassium carbonate (0.30 g) are refluxed in 4 ml of acetonitrile for 1 week. After 1 week, additional dibromobutane (0.21 ml) is added and refluxing is continued for 3 days. The reaction mixture is poured into water, extracted with methylene chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate is purified by flash column chromatography eluting with ethyl acetate/hexane (10/90) to ethyl acetate/hexane (25/75). The appropriate fractions are pooled and concentrated to give the title compound, NMR (300 MHz, CDCl3) 7.78, 6.98, 6.78, 3.52, 3.20-3.10, 1.87 and 1.44δ.

Workup

  1. waitAfter 1 week
  2. temperaturerefluxing
  3. extractionextracted with methylene chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe concentrate is purified by flash column chromatography
  7. washeluting with ethyl acetate/hexane (10/90) to ethyl acetate/hexane (25/75)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-5577ecd3e92b486691e338e2d394c783
Source dataset
uspto-grants-1996_10
Patent number
US05563142

Reaction notes

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