Triethylamine → tert-butyl 4-{[4-({[(3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl]amino}methyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylate

HRID 16580

Reaction equation

HRID 16580 reaction equation
[CH:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[NH:6][C:5]1=[O:13])([CH3:3])[CH3:2].CCN(CC)CC.[NH2:21][CH2:22][CH:23]1[CH2:28][CH2:27][N:26]([CH2:29][C:30]2([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[CH2:25][CH2:24]1.[C:43]([O-])(O)=[O:44].[Na+]>C(Cl)Cl>[CH:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:43]([NH:21][CH2:22][CH:23]2[CH2:28][CH2:27][N:26]([CH2:29][C:30]3([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[CH2:25][CH2:24]2)=[O:44])[C:5]1=[O:13])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 16535801-(Propan-2-yl)-1,3-dihydro-2H-benzimidazol-2-oneHCID 67232551tert-Butyl4-{[4-(aminomethyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylate

Product 1

HCID 68584353tert-butyl 4-{[4-({[(3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl]amino}methyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of p-nitrophenylchloroformate (4.14 g, 0.0205 mol), 1-isopropyl-1,3-dihydro-2H-benzimidazol-2-one (3.62 g, 0.0205 mol, J. Med. Chem. 1999, 42, 2870-2880) and Et3N (7.81 mL, 0.0560 mol) in CH2Cl2 (100 mL) was stirred at room temperature for 4 h. Then, tert-butyl 4-{[4-(aminomethyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylate (5.72 g, 0.0187 mol, step 5) was added, and the resulting mixture was stirred at room temperature for 24 h. The reaction mixture was diluted with sat. NaHCO3 aq. (300 mL), extracted with CH2Cl2 (300 mL) for three times. The combined extract was dried over Na2SO4 and concentrated. The residue was chromatographed on a column of NH-silica gel eluting with hexane/ethyl acetate (1:1) to give 9.83 g (100%) of the title compound as a yellow syrup.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 24 h
  2. extractionextracted with CH2Cl2 (300 mL) for three times
  3. extractionThe combined extract
  4. dry with materialwas dried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was chromatographed on a column of NH-silica gel eluting with hexane/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-b49458cd1d814d27a3393d2ce0833f76
Source dataset
uspto-grants-2010_06
Patent number
US07737163B2

Linked notes

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