4-Methylmorpholine → 1-[[5-[(2,5-Difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridin-2-yl]carbonyl]azetidin-3-ol

To a solution of 1-(diphenylmethyl)azetidin-3-ol (230 mg, 0.961 mmol) in ethanol (10 ml), palladium-carbon (50 mg) was added, and the mixture was stirred for 1.5 hours in a hydrogen atmosphere. The reaction suspension was filtered, and then the filtrate was concentrated under reduced pressure. The resulting concentration residue was dissolved in methylene chloride (10 ml), and 5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxylic acid (113 mg, 0.268 mmol) obtained in Example 12, 1-hydroxybenzotriazole (36 mg, 0.268 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (62 mg, 0.322 mmol) and 4-methylmorpholine (35 μl, 0.322 mmol) were added. The mixture was stirred for 4 days at room temperature. The reaction solution was concentrated under reduced pressure, ethyl acetate was added, and the mixture was washed sequentially with saturated aqueous sodium hydrogencarbonate and saturated brine. The organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. The resulting concentration residue was subjected to silica gel column chromatography, and the fraction obtained from an elution with methanol:methylene chloride (=1:40) was concentrated under reduced pressure, to obtain a solid. The obtained solid was washed with ethanol, and then was collected by filtration to obtain the title compound (72 mg, 0.151 mmol, 56%) as a white powder.

1. filtrationThe reaction suspension was filtered
2. concentrationthe filtrate was concentrated under reduced pressure
3. concentrationThe resulting concentration residue
4. dissolutionwas dissolved in methylene chloride (10 ml)
5. concentrationThe reaction solution was concentrated under reduced pressure, ethyl acetate
6. additionwas added
7. washthe mixture was washed sequentially with saturated aqueous sodium hydrogencarbonate and saturated brine
8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationthe filtrate was concentrated under reduced pressure
11. concentrationThe resulting concentration residue
12. customthe fraction obtained from an elution with methanol
13. concentrationmethylene chloride (=1:40) was concentrated under reduced pressure
14. customto obtain a solid
15. washThe obtained solid was washed with ethanol
16. filtrationwas collected by filtration

ORD-Eintrag

ord-403e08fdf0fe4ca688d230c606d7d302

Quelldatensatz

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08114886B2