Pyridine → HCID 59769523, compound

Temperature

0 °C

To a solution of bis(trichloromethyl)carbonate (0.344 g) in tetrahydrofuran (10 mL) was added dropwise a solution of pyridine (0.281 mL) in tetrahydrofuran (5 mL) under ice-cooling, and stirred for 30 minutes at 0° C. To the reaction solution was added 2-(methylamino)ethyl benzoate hydrochloride (0.750 g) obtained in Reference Synthetic Example 5. A solution of triethylamine (0.485 mL) in tetrahydrofuran (5 mL) was added, and stirred at 0° C. for 1 hr, and further at room temperature for 30 minutes. The reaction solution was concentrated under reduced pressure, and to the residue was added water (30 mL), and then extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with saturated brine (30 mL), and dried over anhydrous sodium sulfate, followed by concentrating under reduced pressure. The resulting oil was dissolved in tetrahydrofuran (5 mL), and the solution was added to a solution of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole (1.0 g), triethylamine (0.808 mL) and 4-dimethylaminopyridine (0.071 g) in tetrahydrofuran (10 mL), and stirred at 40° C. for 18 hrs. The reaction solution was concentrated under reduced pressure, and to the residue was added water (30 mL), and extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with saturated brine (30 mL), and dried over anhydrous sodium sulfate, followed by concentrating under reduced pressure. The residue was purified with silica gel column chromatography (eluted with ethyl acetate:hexane=1:1, then ethyl acetate) to give a mixture of 1:1 of title compound and 2-[[[6-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl]methyl]sulfinyl]-1H-benzimidazol-1-yl]carbonyl](methyl)amino]ethyl benzoate as pale yellow amorphous solid (1.50 g).

1. temperaturecooling
2. customobtained in Reference Synthetic Example 5
3. stirringstirred at 0° C. for 1 hr
4. waitfurther at room temperature for 30 minutes
5. concentrationThe reaction solution was concentrated under reduced pressure
6. additionto the residue was added water (30 mL)
7. extractionextracted with ethyl acetate (50 mL)
8. washThe ethyl acetate layer was washed with saturated brine (30 mL)
9. dry with materialdried over anhydrous sodium sulfate
10. concentrationby concentrating under reduced pressure
11. dissolutionThe resulting oil was dissolved in tetrahydrofuran (5 mL)
12. additionthe solution was added to a solution of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole (1.0 g), triethylamine (0.808 mL) and 4-dimethylaminopyridine (0.071 g) in tetrahydrofuran (10 mL)
13. stirringstirred at 40° C. for 18 hrs
14. concentrationThe reaction solution was concentrated under reduced pressure
15. additionto the residue was added water (30 mL)
16. extractionextracted with ethyl acetate (50 mL)
17. washThe ethyl acetate layer was washed with saturated brine (30 mL)
18. dry with materialdried over anhydrous sodium sulfate
19. concentrationby concentrating under reduced pressure
20. customThe residue was purified with silica gel column chromatography (
21. washeluted with ethyl acetate
22. customhexane=1:1, then ethyl acetate) to give

ORD record

ord-b90ca38700254fd495d65600781ea0b1

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08449911B2