Potassium Carbonate → 1-(3-Methoxy-benzyl)-2-[4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-1H-benzoimidazole-4-carboxylic acid methyl ester

HRID 18551

Reaction equation

HRID 18551 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]2[N:12]=[C:11]([C:14](=[O:29])[NH:15][C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][C:23]4=[O:28])=[CH:18][CH:17]=3)[NH:10][C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4].C([O-])([O-])=O.[K+].[K+].Br[CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([O:44][CH3:45])[CH:39]=1>CN(C=O)C.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[C:13]2[N:12]=[C:11]([C:14](=[O:29])[NH:15][C:16]3[CH:17]=[CH:18][C:19]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][C:23]4=[O:28])=[CH:20][CH:21]=3)[N:10]([CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([O:44][CH3:45])[CH:39]=3)[C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 40672073-Methoxybenzyl bromideHCID 686177922-[4-(3-Oxo-morpholin-4-yl)-phenylcarbamoyl]-1H-benzoimidazole-4-carboxylic acid methyl ester

Product 1

HCID 687910531-(3-Methoxy-benzyl)-2-[4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-1H-benzoimidazole-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

366.5.0 mg (0.929 mmol) 2-[4-(3-Oxo-morpholin-4-yl)-phenylcarbamoyl]-1H-benzoimidazole-4-carboxylic acid methyl ester were dissolved in 15 mL DMF. Sequentially 192.6 mg (1.394 mmol) K2CO3 and 156.1 μl (1.394 mmol) 1-bromomethyl-3-methoxy-benzene were added and the resulting mixture was stirred for 4 h at 80°. The mixture was diluted with 300 mL toluene and washed with 50 mL of a saturated NaHCO3-solution. The product was not completely soluble in toluene, so ethyl acetate had to be added. The organic layer was washed with brine, dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by preparative HPLC (CH3CN/H2O gradient+0.05% formic acid) (separation of isomers) to give 1-(3-Methoxy-benzyl)-2-[4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-1H-benzoimidazole-4-carboxylic acid methyl ester as a light brown amorphous solid.

Workup

  1. washwashed with 50 mL of a saturated NaHCO3-solution
  2. additionto be added
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by preparative HPLC (CH3CN/H2O gradient+0.05% formic acid) (separation of isomers)

Sources & evidence

ORD record
ord-c399fa340ace4eee80e2b9f786f205b2
Source dataset
uspto-grants-2010_06
Patent number
US07741341B2

Linked notes

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