Reaktion #46831

Reaktionsgleichung

5-(2-hydroxy-ethanesulfonyl)-1H-benzoimidazole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide

CH3CN H2O

2-bromo-N-(5-chloro-pyridin-2-yl)-acetamide

→

1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-(2-hydroxy-ethanesulfonyl)-1H-benzoimidazole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide

1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-6-(2-hydroxy-ethanesulfonyl)-1H-benzoimidazole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide

Lösungsmittel

formic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONa 1:1 mixture of both isomers
2. 2
   SonstigeThese isomers could be separated by NP-HPLC
3. 3
   workup.ADDITIONa mixture of heptane, ethanol, methanol and diethyl amine as solvent

Vorschrift

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.

Quelle