Triethylamine → CJ-040714

HRID 502897Notes

Reaction equation

HRID 502897 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].C(N(CC)CC)C.Cl[C:22](Cl)([O:24]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:33][CH2:34][CH:35]1[CH2:40][CH2:39][N:38]([CH2:41][C:42]2([OH:48])[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)[CH2:37][CH2:36]1.C([O-])(O)=O.[Na+]>O1CCCC1>[OH:48][C:42]1([CH2:41][N:38]2[CH2:39][CH2:40][CH:35]([CH2:34][NH:33][C:22]([N:6]3[C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=4[N:4]([CH:1]([CH3:3])[CH3:2])[C:5]3=[O:13])=[O:24])[CH2:36][CH2:37]2)[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1

Participants

7

Reactant 5

HCID 8471Triethylamine2×HCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 16535801-(Propan-2-yl)-1,3-dihydro-2H-benzimidazol-2-oneHCID 592550572H-Pyran-4-ol, 4-[[4-(aminomethyl)-1-piperidinyl]methyl]tetrahydro-

Product 1

HCID 11350913CJ-040714Yield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
80 °C

Procedure

To a stirred mixture of 1-isopropyl-1,3-dihydro-2H-benzimidazol-2-one (J. Med. Chem. 1999, 42, 2870-2880) (23.0 g, 130 mmol) and triethylamine (54.6 mL, 392 mmol) in tetrahydrofuran (300 mL) was added triphosgen (38.8 g, 130 mmol) in tetrahydrofuran (200 mL) gradually at room temperature. Then, the mixture was heated at 80° C. for 4 h. After cooling, a solution of 4-{[4-(aminomethyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-ol (step 2 of Example 1) (24.9 g, 109 mmol) and triethylamine (45 mL, 109 mmol) in tetrahydrofuran (500 mL) was added to the mixture. Then, the mixture was heated at 80° C. for 6 h. After cooling, sat. NaHCO3 aq was added to the mixture. The mixture was extracted with ethyl acetate (500 mL×4). The extracts were washed with 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 31.3 g (67%) of the title compound as a white solid.

Workup

  1. temperatureAfter cooling
  2. temperatureThen, the mixture was heated at 80° C. for 6 h
  3. temperatureAfter cooling
  4. extractionThe mixture was extracted with ethyl acetate (500 mL×4)
  5. washThe extracts were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was chromatographed on a column of aminopropyl-silica gel eluting with hexane/ethyl acetate (3:1)

Sources & evidence

ORD record
ord-8a520a7aa4c74272aa5dfdb2c5a6ccc7
Source dataset
uspto-grants-2010_08
Patent number
US07776885B2

Reaction notes

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