1,1'-Carbonyldiimidazole → 3-{4-[3-(1-Methyl-1H-benzoimidazol-2-yl)-phenyl]-piperazine-1-carbonyl}-morpholine-4-carboxylic acid tert-butyl ester

HRID 2047376Notes

Reaction equation

HRID 2047376 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH:9]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.Cl.[CH3:31][N:32]1[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=2[N:34]=[C:33]1[C:41]1[CH:46]=[CH:45][CH:44]=[C:43]([N:47]2[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]2)[CH:42]=1.CCN(C(C)C)C(C)C>C(#N)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH:9]1[C:14]([N:50]1[CH2:51][CH2:52][N:47]([C:43]2[CH:44]=[CH:45][CH:46]=[C:41]([C:33]3[N:32]([CH3:31])[C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=4[N:34]=3)[CH:42]=2)[CH2:48][CH2:49]1)=[O:16])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 27601334-(tert-Butoxycarbonyl)morpholine-3-carboxylic acidHCID 686704331-Methyl-2-(3-piperazin-1-yl-phenyl)-1H-benzoimidazole dihydrochloride

Product 1

HCID 686711193-{4-[3-(1-Methyl-1H-benzoimidazol-2-yl)-phenyl]-piperazine-1-carbonyl}-morpholine-4-carboxylic acid tert-butyl esterYield 40%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of morpholine-3,4-dicarboxylic acid-4-tert-butyl ester (0.16 g, 0.71 mmol) in acetonitrile (8 mL) was added CDI (0.16 g, 0.71 mmol) and the resulting suspension was stirred at room temperature overnight. 1-Methyl-2-(3-piperazin-1-yl-phenyl)-1H-benzoimidazole dihydrochloride (0.20 g, 0.55 mmol) (obtained as described in method C) and DIPEA (0.19 mL, 1.10 mmol) were added and the resulting solution heated at 65° C. overnight. The reaction was then cooled to room temperature, the solvent removed, the crude product was dissolved with 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: gradient from cyclohexane to cyclohexane:EtOAc 2:1) to afford 0.11 g (40%) 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
  4. dissolutionthe crude product was dissolved with 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: gradient from cyclohexane to cyclohexane:EtOAc 2:1)

Sources & evidence

ORD record
ord-ee294754f091400fb7b0500efc33878d
Source dataset
uspto-grants-2013_11
Patent number
US08592463B2

Reaction notes

Loading…