tert-butyl (3S,5R)-3-{[({2-[(4-methoxybutyl)amino]phenyl}amino)(oxo)acetyl](2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate → tert-butyl (3S,5R)-3-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

HRID 2168893Notes

Reaction equation

HRID 2168893 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15](=O)[C:16]([N:18]([CH2:40][CH:41]([CH3:43])[CH3:42])[C@H:19]1[CH2:24][C@@H:23]([C:25]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[O:26])[CH2:22][N:21]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:20]1)=[O:17]>C(O)(=O)C>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[N:14]=[C:15]1[C:16]([N:18]([CH2:40][CH:41]([CH3:42])[CH3:43])[C@H:19]1[CH2:24][C@@H:23]([C:25]([N:27]2[CH2:28][CH2:29][O:30][CH2:31][CH2:32]2)=[O:26])[CH2:22][N:21]([C:33]([O:35][C:36]([CH3:39])([CH3:37])[CH3:38])=[O:34])[CH2:20]1)=[O:17]

Participants

3

Reactant 1

HCID 58355596tert-butyl (3S,5R)-3-{[({2-[(4-methoxybutyl)amino]phenyl}amino)(oxo)acetyl](2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

Product 1

HCID 58355127tert-butyl (3S,5R)-3-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylateYield 66.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
80 °C

Procedure

tert-Butyl (3S,5R)-3-{[({2-[(4-methoxybutyl)amino]phenyl}amino) (oxo) acetyl](2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (9.11 g) was dissolved in acetic acid (50 ml), and the mixture was stirred at 80° C. for 15 hr. The reaction mixture was cooled to room temperature and concentrated under reduced pressure, the residue was diluted with aqueous sodium bicarbonate, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to basic silica gel column chromatography, and a fraction eluted with ethyl acetate was concentrated under reduced pressure to give tert-butyl (3S,5R)-3-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (5.85 g), and a fraction eluted with ethyl acetate-methanol (85:15) was concentrated under reduced pressure to give 1-(4-methoxybutyl)-N-(2-methylpropyl)-N-[(3S,5R)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl]-1H-benzimidazole-2-carboxamide (580 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. additionthe residue was diluted with aqueous sodium bicarbonate
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. washa fraction eluted with ethyl acetate
  9. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-8cc58880d55945dc9bc2a1fbcdf9e304
Source dataset
uspto-grants-2015_06
Patent number
US09045436B2

Reaction notes

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