Cyclopropanecarboxylic acid → cyclopropyl-{4-[3-(1-methyl-1H-benzoimidazol-2-yl)-phenyl]-piperazin-1-yl}-methanone

HRID 2047374Notes

Reaction equation

HRID 2047374 reaction equation
[CH:1]1([C:4]([OH:6])=O)[CH2:3][CH2:2]1.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.Cl.[CH3:21][N:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[N:24]=[C:23]1[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([N:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)[CH:32]=1>C(#N)C>[CH:1]1([C:4]([N:40]2[CH2:41][CH2:42][N:37]([C:33]3[CH:34]=[CH:35][CH:36]=[C:31]([C:23]4[N:22]([CH3:21])[C:26]5[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=5[N:24]=4)[CH:32]=3)[CH2:38][CH2:39]2)=[O:6])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 15655Cyclopropanecarboxylic acidHCID 682631,1'-CarbonyldiimidazoleHCID 686704331-Methyl-2-(3-piperazin-1-yl-phenyl)-1H-benzoimidazole dihydrochloride

Product 1

HCID 68671116cyclopropyl-{4-[3-(1-methyl-1H-benzoimidazol-2-yl)-phenyl]-piperazin-1-yl}-methanoneYield 85.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of cyclopropanecarboxylic acid (0.06 g, 0.68 mmol) in acetonitrile (8 mL) was added CDI (0.11 g, 0.68 mmol) and the resulting suspension was stirred at room temperature for 5 h. 1-Methyl-2-(3-piperazin-1-yl-phenyl)-1H-benzoimidazole dihydrochloride (0.20 g, 0.55 mmol) was added and the resulting solution heated at 65° C. overnight. The reaction was then cooled to room temperature, the solvent removed under reduced pressure. The crude product was redissolved in dichloromethane (15 mL) and washed with saturated NaHCO3 solution (2×3 mL) The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (eluent: cyclohexane:EtOAc, gradient from 100% cyclohexane to 100% ethyl acetate) to afford 0.17 g (85%) of the title compound.

Workup

  1. temperaturethe resulting solution heated at 65° C. overnight
  2. temperatureThe reaction was then cooled to room temperature
  3. customthe solvent removed under reduced pressure
  4. dissolutionThe crude product was redissolved in dichloromethane (15 mL)
  5. washwashed with saturated NaHCO3 solution (2×3 mL) The organic layer
  6. dry with materialwas dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography (eluent: cyclohexane:EtOAc, gradient from 100% cyclohexane to 100% ethyl acetate)

Sources & evidence

ORD record
ord-1c01f9252fe94edeb073a4b3f83cbbce
Source dataset
uspto-grants-2013_11
Patent number
US08592463B2

Reaction notes

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