Toluene → 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid methyl ester

HRID 18520Notes

Reaction equation

HRID 18520 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]2[N:12]=[C:11]([C:14](=[O:25])[N:15](C(C)C)[CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[NH:10][C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4].C([O-])([O-])=O.[K+].[K+].Br[CH2:33][C:34]([NH:36][C:37]1[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][N:38]=1)=[O:35].[C:44]1(C)[CH:49]=CC=C[CH:45]=1>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[C:13]2[N:12]=[C:11]([C:14](=[O:25])[NH:15][CH:16]3[CH2:21][CH2:20][N:19]([CH:44]([CH3:49])[CH3:45])[CH2:18][CH2:17]3)[N:10]([CH2:33][C:34](=[O:35])[NH:36][C:37]3[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][N:38]=3)[C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4]

Participants

6

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 34211102-Bromo-N-(5-chloro-2-pyridinyl)acetamideHCID 686173622-(Isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid methyl ester

Product 1

HCID 114664091-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

100.8 mg (0.29 mmol) 2-(Isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid methyl ester were dissolved in 6 mL DMF. Subsequently 60.6 mg (0.44 mmol) K2CO3 and 87.5 mg (0.35 mmol) 2-bromo-N-(5-Chloro-pyridin-2-yl-)-acetamide were added and the resulting mixture was stirred for 3 h at 80° C. The reaction mixture was diluted with 60 mL toluene and washed with a sat. NaHCO3 solution and brine. The organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by preparative HPLC (CH3CN/H2O gradient+0.05% formic acid) to give 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid methyl ester as a white amorphous solid. The product was obtained as its hydroformiate.

Workup

  1. washwashed with a sat. NaHCO3 solution and brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. customthe solvent was removed under reduced pressure
  4. customThe residue was purified by preparative HPLC (CH3CN/H2O gradient+0.05% formic acid)

Sources & evidence

ORD record
ord-9741d861ddb9467e980db0243530e544
Source dataset
uspto-grants-2010_06
Patent number
US07741341B2

Reaction notes

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