Triethylamine → 5-fluoro-N-({1-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidin-4-yl}methyl)-3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-carboxamide

HRID 502904Notes

Reaction equation

HRID 502904 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:9][C:8](=[O:10])[N:7]([CH:11]([CH3:13])[CH3:12])[C:6]=2[CH:14]=1.C(N(CC)CC)C.[NH2:22][CH2:23][CH:24]1[CH2:29][CH2:28][N:27]([CH2:30][C:31]2([OH:37])[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[CH2:26][CH2:25]1.[C:38](OCC)(=[O:40])C>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]([C:38]([NH:22][CH2:23][CH:24]3[CH2:29][CH2:28][N:27]([CH2:30][C:31]4([OH:37])[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)[CH2:26][CH2:25]3)=[O:40])[C:8](=[O:10])[N:7]([CH:11]([CH3:12])[CH3:13])[C:6]=2[CH:14]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 194378886-fluoro-1-(propan-2-yl)-2,3-dihydro-1H-1,3-benzodiazol-2-oneHCID 592550572H-Pyran-4-ol, 4-[[4-(aminomethyl)-1-piperidinyl]methyl]tetrahydro-

Product 1

HCID 594281835-fluoro-N-({1-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidin-4-yl}methyl)-3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-carboxamideYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred mixture of 6-fluoro-1-isopropyl-1,3-dihydro-2H-benzimidazol-2-one (Step 2 of Example 9, 0.58 g, 3 mmol) and p-nitrophenylchloroformate (0.66 g, 3.3 mmol) in dichloromethane (15 mL) was added triethylamine (1.25 mL, 9.0 mmol) at room temperature. After being stirred for 2 h, a solution of 4-{[4-(aminomethyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-ol (Step 2 of Example 1, 0.75 g, 3.3 mmol) in dichloromethane (15 mL) was added to the mixture. After being stirred for 4 h, the mixture was diluted with ethyl acetate (100 mL). Then, the organic layer was washed with 0.5 N NaOH aq. (10 mL) for 5 times and brine, dried over MgSO4 and concentrated. The residue was chromatographed on a column of aminopropyl-silica gel eluting with hexane/ethyl acetate (3:1) to give 0.97 g (79%) of the title compound as a white solid.

Workup

  1. stirringAfter being stirred for 4 h
  2. washThen, the organic layer was washed with 0.5 N NaOH aq. (10 mL) for 5 times and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was chromatographed on a column of aminopropyl-silica gel eluting with hexane/ethyl acetate (3:1)

Sources & evidence

ORD record
ord-1c94a6ccd7964d4784e9f6a6472e7ed4
Source dataset
uspto-grants-2010_08
Patent number
US07776885B2

Reaction notes

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