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

HRID 1368593

Reaction equation

HRID 1368593 reaction equation
C([O:4][CH2:5][CH2:6][O:7][C:8]1[C:12]([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)=[C:11]([NH2:20])[N:10]([CH3:21])[N:9]=1)(=O)C.[CH:22]([C:25]1[CH:26]=[CH:27][C:28]([S:31](Cl)(=[O:33])=[O:32])=[N:29][CH:30]=1)([CH3:24])[CH3:23].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[OH:4][CH2:5][CH2:6][O:7][C:8]1[C:12]([C:13]2[CH:14]=[CH:15][C:16]([CH3:19])=[CH:17][CH:18]=2)=[C:11]([NH:20][S:31]([C:28]2[CH:27]=[CH:26][C:25]([CH:22]([CH3:24])[CH3:23])=[CH:30][N:29]=2)(=[O:32])=[O:33])[N:10]([CH3:21])[N:9]=1

Participants

6

Reactant 3

HCID 311Citric AcidHCID 222819185-Isopropylpyridine-2-sulfonyl chlorideHCID 222820022-{[5-amino-1-methyl-4-(4-methylphenyl)-1H-pyrazol-3-yl]oxy}ethyl acetate

Product 1

HCID 22282040N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-isopropyl-2-pyridinesulfonamideYield 47.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-e094230d614c438e953cee2d5c41885a
Source dataset
uspto-grants-2003_06
Patent number
US06573270B1

Linked notes

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