Water → 4-[2-(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]benzonitrile

HRID 2173439Notes

Reaction equation

HRID 2173439 reaction equation
Br[CH2:2][CH2:3][C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=1.Cl.[N:13]1([C:19](=[O:32])[CH2:20][C:21]2[CH:26]=[CH:25][C:24]([N:27]3[CH:31]=[N:30][N:29]=[N:28]3)=[CH:23][CH:22]=2)[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[K+].[K+].O>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[N:27]1([C:24]2[CH:25]=[CH:26][C:21]([CH2:20][C:19]([N:13]3[CH2:14][CH2:15][N:16]([CH2:2][CH2:3][C:4]4[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=4)[CH2:17][CH2:18]3)=[O:32])=[CH:22][CH:23]=2)[CH:31]=[N:30][N:29]=[N:28]1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 128865484-(2-Bromoethyl)benzonitrileHCID 675172361-(piperazin-1-yl)-2-[4-(1H-tetrazol-1-yl)phenyl]ethanone hydrochloride

Product 1

HCID 675182214-[2-(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]benzonitrile

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

Combined 4-(2-bromoethyl)benzonitrile (68 mg, 0.32 mmol) with 1-(piperazin-1-yl)-2-[4-(1H-tetrazol-1-yl)phenyl]ethanone hydrochloride (100 mg, 0.324 mmol), tetrabutyl ammonium iodide (120 mg, 0.324 mmol) and potassium carbonate (179 mg, 1.30 mmol) in DMF (2 mL) and stirred at 80° C. overnight. The reaction mixture was poured into water and extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. After initial purification by HPLC, repurification by preparative TLC eluting with 5% of 1:9 NH4OH/methanol in DCM afforded the title compound. LC/MS: [(M+1)]+=402.

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customAfter initial purification
  7. customby HPLC, repurification by preparative TLC
  8. washeluting with 5% of 1:9 NH4OH/methanol in DCM

Sources & evidence

ORD record
ord-1fca07c678864ed1809c25601ba223c5
Source dataset
uspto-grants-2015_06
Patent number
US09056859B2

Reaction notes

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