Dimethylformamide → HCID 59331560, compound

To a solution of 6-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridine-3-carboxylic acid (0.500 g) in N,N-dimethylformamide (10 mL) were added N-methoxymethanamine hydrochloride (152 mg), triethylamine (0.436 mL), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (300 mg) and 1-hydroxybenzotriazole (239 mg), and the mixture was stirred at room temperature for 16 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=30:70-100:0, volume ratio) to give a colorless oil. A solution of the obtained oil in tetrahydrofuran (5 mL) was purged with nitrogen, and a 1.0M methylmagnesium bromide tetrahydrofuran solution (1.5 mL) was added under ice-cooling. The reaction solution was warmed to room temperature, and stirred at room temperature for 16 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=30:70-100:0, volume ratio) to give a colorless oil. A solution of the obtained oil in tetrahydrofuran (3 mL) was purged with nitrogen, a 1.0M methylmagnesium bromide tetrahydrofuran solution (5.0 mL) was added under ice-cooling, and the mixture was stirred at 0° C. for 4 hr. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=30:70-100:0, volume ratio) and recrystallized from hexane-ethyl acetate to give the title compound (0.096 g, yield 19%) as colorless crystals. MS: 495 (MH+). melting point 112-114° C.

1. extractionthe mixture was extracted with ethyl acetate
2. washThe extract was washed successively with water and saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=30:70-100:0, volume ratio)
6. customto give a colorless oil
7. customA solution of the obtained oil in tetrahydrofuran (5 mL) was purged with nitrogen
8. additiona 1.0M methylmagnesium bromide tetrahydrofuran solution (1.5 mL) was added under ice-
9. temperaturecooling
10. temperatureThe reaction solution was warmed to room temperature
11. stirringstirred at room temperature for 16 hr
12. additionWater was added to the reaction mixture
13. extractionthe mixture was extracted with ethyl acetate
14. washThe extract was washed successively with water and saturated brine
15. dry with materialdried over anhydrous magnesium sulfate
16. concentrationconcentrated under reduced pressure
17. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=30:70-100:0, volume ratio)
18. customto give a colorless oil
19. customA solution of the obtained oil in tetrahydrofuran (3 mL) was purged with nitrogen
20. additiona 1.0M methylmagnesium bromide tetrahydrofuran solution (5.0 mL) was added under ice-
21. temperaturecooling
22. stirringthe mixture was stirred at 0° C. for 4 hr
23. additionA saturated aqueous ammonium chloride solution was added to the reaction mixture
24. extractionthe mixture was extracted with ethyl acetate
25. washThe extract was washed successively with water and saturated brine
26. dry with materialdried over anhydrous magnesium sulfate
27. concentrationconcentrated under reduced pressure
28. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=30:70-100:0, volume ratio)
29. customrecrystallized from hexane-ethyl acetate

ORD record

ord-f79ba98f8132423da0d290d09415a138

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08318746B2