2-Bromo-N-(5-chloro-2-pyridinyl)acetamide → 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-(2-hydroxy-ethanesulfonyl)-1H-benzoimidazole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide

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Reaction Steps

1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-(2-hydroxy-ethanesulfonyl)-1H-benzoimidazole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide and 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-6-(2-hydroxy-ethanesulfonyl)-1H-benzoimidazole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide were prepared by a procedure according to example 29 starting from 1 g (2.5 mmol) crude 5-(2-hydroxy-ethanesulfonyl)-1H-benzoimidazole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide and 758.9 mg (3.04 mmol) 2-bromo-N-(5-chloro-pyridin-2-yl)-acetamide. Preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid) gave a 1:1 mixture of both isomers described in the title. These isomers could be separated by NP-HPLC using a chiral stationary phase and a mixture of heptane, ethanol, methanol and diethyl amine as solvent. Structural assignment of both isomers was achieved by NOE-spectroscopy.

Provenance & Evidence