Water → methyl 2-chloro-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylate

HRID 44545Notes

Reaction equation

HRID 44545 reaction equation
[Cl:1][C:2]1[NH:6][C:5]2[C:7]([C:17]([O:19][CH3:20])=[O:18])=[CH:8][C:9]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:10][C:4]=2[N:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[C:30]=1[CH3:39].O>CN(C)C=O>[Cl:1][C:2]1[N:3]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:36])([F:37])[F:38])[C:30]=2[CH3:39])[C:4]2[CH:10]=[C:9]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[CH:8]=[C:7]([C:17]([O:19][CH3:20])=[O:18])[C:5]=2[N:6]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27756171-(Bromomethyl)-2-methyl-3-(trifluoromethyl)benzeneHCID 178498371HCID 178498371, compound

Product 1

HCID 56960545methyl 2-chloro-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylateYield 83%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To the mixture of methyl 2-chloro-5-(4-morpholinyl)-1H-benzimidazole-7-carboxylate, prepared as described in Example 65 (0.5 g, 1.691 mmol) in N,N-Dimethylformamide (DMF) (10 ml) was added in potassium carbonate (0.467 g, 3.38 mmol) and 1-(bromomethyl)-2-methyl-3-(trifluoromethyl)benzene (0.428 g, 1.691 mmol). The reaction mixture was stirred at 80° C. for 1 h. The reaction was cooled down. Water (100 mL) was added in. The solid precipitated. Filtration gave the solid which was purified on a silica column (20˜60% EtOAc/Hexane) to give the product as white solid (0.66 g, 83%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.54 (s, 3H) 3.07-3.16 (m, 4H) 3.68-3.78 (m, 4H) 3.91 (s, 3H) 5.63 (s, 2H) 6.41 (d, J=7.83 Hz, 1H) 7.28 (t, J=7.83 Hz, 1H) 7.39 (d, J=2.27 Hz, 1H) 7.50 (d, J=2.53 Hz, 1H) 7.63 (d, 1H). MS (ES+) m/e 468.0 [M+H]+.

Workup

  1. customprepared
  2. temperatureThe reaction was cooled down
  3. customThe solid precipitated
  4. filtrationFiltration
  5. customgave the solid which
  6. customwas purified on a silica column (20˜60% EtOAc/Hexane)

Sources & evidence

ORD record
ord-271d8bbd60d842e1aa4d053b743bbce6
Source dataset
uspto-grants-2013_09
Patent number
US08541411B2

Reaction notes

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