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

Participants

Reaction Steps

325.1 mg (0.57 mmol) 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid were dissolved in 20 mL CH2Cl2. Subsequently 470 μl (5.7 mmol) cyclopropyl-methanol, 152.2 mg (0.74 mmol) DCC and 6.9 mg DMAP were added. The resulting mixture was stirred at room temperature for 16 h. The next day further 100 μl (2.28 mmol) cyclopropyl-methanol, 58.6 mg (0.29 mmol) DCC and 20 mg DMAP were added and the reaction mixture was stirred for 48 h. The solvent was removed under vacuo. Final purification by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid) gave 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid cyclopropylmethyl ester as a white amorphous solid. The corresponding acetate was obtained by the following procedure: The above described material was dissolved in CH2Cl2 and washed with a saturated NaHCO3-solution. The organic layer was dried over anhydrous MgSO4 and concentrated. The resulting residue was diluted in 20 mL water containing 4 equiv. AcOH and lyophilized.

Provenance & Evidence