Diisopropylethylamine → HCID 59331581, compound

To a solution (30 mL) of 2-[4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanic acid in N,N-dimethylformamide were added N,N-diisopropylethylamine (1.89 mL), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo(4,5-b)pyridinium 3-oxide hexafluorophosphate (1.52 g) and 5-cyclobutylisoxazol-4-amine hydrochloride (0.669 g), and the mixture was stirred at room temperature for 20 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 sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=70:30-100:0, volume ratio). The obtained crude product was dissolved in ethanol (30 mL), palladium carbon (1.00 g) was added, and the mixture was purged with hydrogen (5 atm) and stirred at room temperature for 2 hr and at 50° C. for 2 hr. The reaction mixture was filtered to remove the catalyst, sodium hydroxide (0.160 g) was added to the filtrate, and the mixture was heated under reflux for 1.5 hr. To the reaction mixture was added ammonium chloride (0.243 g), and the mixture was cooled to room temperature and stirred at room temperature for 16 hr. The reaction mixture was concentrated, the obtained residue was suspended in acetone and the suspension was filtered to remove insoluble materials. The filtrate was concentrated, and the obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=60:40-100:0, volume ratio) to give the title compound (0.720 g, yield of 3 steps 45%) as a colorless oil. MS: 441 (MH+).

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 sodium sulfate
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=70:30-100:0, volume ratio)
6. customThe obtained crude product
7. customthe mixture was purged with hydrogen (5 atm)
8. stirringstirred at room temperature for 2 hr and at 50° C. for 2 hr
9. filtrationThe reaction mixture was filtered
10. customto remove the catalyst, sodium hydroxide (0.160 g)
11. additionwas added to the filtrate
12. temperaturethe mixture was heated
13. temperatureunder reflux for 1.5 hr
14. additionTo the reaction mixture was added ammonium chloride (0.243 g)
15. temperaturethe mixture was cooled to room temperature
16. stirringstirred at room temperature for 16 hr
17. concentrationThe reaction mixture was concentrated
18. filtrationthe suspension was filtered
19. customto remove insoluble materials
20. concentrationThe filtrate was concentrated
21. customthe obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=60:40-100:0, volume ratio)

ORD record

ord-31030736eb674f4497508ae898de8238

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08318746B2