Pyridine → HCID 23071203, compound

To a solution of bis(trichloromethyl)carbonate (0.174 g) in tetrahydrofuran (8 mL) was added dropwise a solution of pyridine (0.146 mL) in tetrahydrofuran (1 mL) under ice-cooling. The reaction solution was stirred for 1 hr under ice-cooling, and ethyl 2-(methylamino)ethyl carbonate hydrochloride (0.330 g) obtained in Reference Synthetic Example 14 was added thereto. A solution of triethylamine (0.250 mL) in tetrahydrofuran (1 mL) was added dropwise, and stirred at room temperature for 3 hrs. The reaction solution was concentrated under reduced pressure, and to the residue was added water (10 mL), and then extracted with ethyl acetate (30 mL). The ethyl acetate layer was washed with saturated brine (10 mL), and dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure, and the residue was dissolved in tetrahydrofuran (8 mL). To the solution were added 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole (0.432 g), triethylamine (0.279 mL) and 4-dimethylaminopyridine (0.008 g), and stirred at 60° C. for 17.5 hrs. The reaction solution was concentrated under reduced pressure, and to the residue was added water (20 mL), and extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with saturated brine (10 mL), and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was purified with basic silica gel column chromatography (eluted with ethyl acetate:hexane=1:2, then 1:1), and further with silica gel column chromatography (eluted with ethyl acetate:hexane=2:1, then ethyl acetate) to give a mixture of 1:1 of title compound and 2-[[[6-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl]-1H-benzimidazol-1-yl]carbonyl]methylamino]ethyl ethyl carbonate as pale yellow amorphous solid (0.09 g).

1. temperaturecooling
2. temperaturecooling

ORD record

ord-6aec370e4dee42c2a9e9dbdcf4737728

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08449911B2