Reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[F:15].C([O-])(O)=[O:17].[Na+].[CH3:21][O:22][C:23]([C:25]1[C:33]2[N:32]=[C:31]([C:34](Cl)(Cl)Cl)[NH:30][C:29]=2[CH:28]=[CH:27][CH:26]=1)=[O:24]>C1COCC1.O.C(Cl)Cl>[CH3:21][O:22][C:23]([C:25]1[C:33]2[N:32]=[C:31]([C:34](=[O:17])[NH:1][C:2]3[CH:7]=[CH:6][C:5]([C:8]([N:10]4[CH2:14][CH2:13][CH2:12][CH2:11]4)=[O:9])=[CH:4][C:3]=3[F:15])[NH:30][C:29]=2[CH:28]=[CH:27][CH:26]=1)=[O:24]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Procedure
59.0 mg (0.28 mmol) (4-Amino-3-fluoro-phenyl)-pyrrolidin-1-yl-methanone was dissolved in 6 mL THF and 3 mL water. 238.0 mg (2.83 mmol) NaHCO3 were added. Finally 75.6 mg (0.26 mmol) 2-Trichloromethyl-1H-benzoimidazole-4-carboxylic acid methyl ester were added and the resulting mixture was stirred vigorously for 3 h at RT. The mixture was diluted with 25 mL CH2Cl2 and washed with a saturated NaHCO3-solution and with brine. The organic layer was dried over anhydrous MgSO4 and concentrated under reduced pressure. After purification by preparative RP-HPLC (CH3CN/H2O gradient and 0.05% formic acid) pure 2-[2-Fluoro-4-(pyrrolidine-1-carbonyl)-phenylcarbamoyl]-1H-benzoimidazole-4-carboxylic acid methyl ester was obtained in form of a colorless amorphous solid.
Workup
- washwashed with a saturated NaHCO3-solution and with brine
- dry with materialThe organic layer was dried over anhydrous MgSO4
- concentrationconcentrated under reduced pressure
- customAfter purification by preparative RP-HPLC (CH3CN/H2O gradient and 0.05% formic acid) pure 2-[2-Fluoro-4-(pyrrolidine-1-carbonyl)-phenylcarbamoyl]-1H-benzoimidazole-4-carboxylic acid methyl ester
- customwas obtained in form of a colorless amorphous solid
Sources & evidence
- ORD record
- ord-87f27d586a1c44ff9b958c8c69d2a23d
- Source dataset
- uspto-grants-2010_06
- Patent number
- US07741341B2
Linked notes
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