HCID 54164551, compound → HCID 22100648, compound

Participants

Reaction Steps

To a mixture of 1-tert-butoxycarbonyl-2-methyl-5-methoxycarbonyl-6-(N-(tert-butoxycarbonyl)piperidin-4-yloxy)benzimidazole and 1-tert-butoxycarbonyl-2-methyl-6-methoxycarbonyl-5-(N-(tert-butoxycarbonyl)piperidin-4-yloxy)benzimidazole (2.5 g) in methanol (200 mL) was bubbled in ammonia at 0° C. After stirring for 2 hours at ambient temperature the reaction mixture was concentrated. The resulting residue was purified by silica gel chromatography (hexane/ethyl acetate/CH2 Cl2 /methanol, gradient) to afford 2-methyl-5-methoxycarbonyl-6-(N-(tert-butoxycarbonyl)piperidin-4-yloxy)benzimidazole. To this product (0.66 g) in DMF (20 mL) was added NaH (0.075 g) at ambient temperature. After stirring at ambient temperature for 30 minutes 7-bromomethyl-2-naphthonitrile (0.5 g) was added at 0° C. The reaction mixture was stirred at ambient temperature for 0.5 hours. The reaction was worked up between ethyl acetate and H2O. The organic layer was dried and concentrated to afford a mixture of 1-(4-cyanonaphth-1-yl)methyl-2-methyl-5-methoxycarbonyl-6-(N-(tert-butoxycarbonyl)piperidin-4-yloxy)benzimidazole and 1-(4-cyanonaphth-1-yl)methyl-2-methyl-6-methoxycarbonyl-5-(N-(tert-butoxycarbonyl)piperidin-4-yloxy)benzimidazole in a ratio of 2 to 1, respectively.

Provenance & Evidence