Citric Acid → N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-isopropyl-2-pyridinesulfonamide

To a solution of 2-{[5-amino-1-methyl-4-(4-methylphenyl)-1H-pyrazol-3-yl]oxy}ethyl acetate (Preparation 5) (3.80 g) in anhydrous pyridine (25 ml) at room temperature and under an atmosphere of nitrogen was added 4-dimethylaminopyridine (0.85 g) and 5-isopropyl-2-pyridinesulfonyl chloride (2.00 g). After being left to stir overnight, the reaction mixture was poured onto saturated citric acid solution (300 ml) and extracted with ethyl acetate (2×200 ml). The organic fractions were washed with brine (200 ml), dried over magnesium sulfate, filtered and concentrated under reduced pressure. To a solution of the residue (4.45 g) in ethanol (100 ml) was added sodium hydroxide solution (2.76 g in 10 ml water). The red solution which formed was stirred for 1 hour before being concentrated to approximately 20 ml under reduced pressure and partitioned between ethyl acetate (2×100 ml) and saturated citric acid solution (100 ml). Washing of the organic fractions with brine (100 ml), drying over magnesium sulfate, filtering and concentration under reduced pressure afforded a brown residue. Purification by column chromatography on silica gel (200 g), eluting in an isocratic fashion with dichloromethane:methanol (20:1) afforded the title compound as a brown foam (1.85 g).

1. waitAfter being left
2. extractionextracted with ethyl acetate (2×200 ml)
3. washThe organic fractions were washed with brine (200 ml)
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. additionTo a solution of the residue (4.45 g) in ethanol (100 ml) was added sodium hydroxide solution (2.76 g in 10 ml water)
8. customThe red solution which formed
9. stirringwas stirred for 1 hour
10. concentrationbefore being concentrated to approximately 20 ml under reduced pressure
11. custompartitioned between ethyl acetate (2×100 ml) and saturated citric acid solution (100 ml)
12. washWashing of the organic fractions with brine (100 ml)
13. dry with materialdrying over magnesium sulfate
14. filtrationfiltering
15. concentrationconcentration under reduced pressure
16. customafforded a brown residue
17. customPurification by column chromatography on silica gel (200 g)
18. washeluting in an isocratic fashion with dichloromethane:methanol (20:1)

ORD 기록

ord-0140a0afed8d4b33b9d1e3bce6d69cf6

출처 데이터셋

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06962923B2