Reaction #1149920

Reaction equation

2-{[5-amino-4-(1,3-benzodioxol-5-yl)-1-methyl-1H-pyrazol-3-yl]oxy}ethyl acetate

5-isopropyl-2-pyridinesulfonyl chloride

citric acid

→

title compound

Yield 2.5%

N-[4-(1,3-benzodioxol-5-yl)-3-(2-hydroxyethoxy)-1-methyl-1H-pyrazol-5-yl]-5-isopropyl-2-pyridinesulfonamide

Yield 2.5%

Solvents

pyridine

Conditions

Workup

1. 1
   workup.WAITAfter being left
2. 2
   Temperatureto reflux overnight
3. 3
   Extractionextracted with ethyl acetate (2×50 ml)
4. 4
   WashThe organic fractions were washed with brine (50 ml)
5. 5
   Dryingby drying over magnesium sulfate
6. 6
   Filtrationfiltering
7. 7
   Concentrationconcentration under reduced pressure
8. 8
   workup.ADDITIONTo a solution of the residue in ethanol (50 ml) was added sodium hydroxide solution (5 ml of 2M)
9. 9
   Concentrationbefore being concentrated to approximately 5 ml under reduced pressure
10. 10
    Otherpartitioned between ethyl acetate (2×100 ml) and saturated citric acid solution (100 ml)
11. 11
    WashWashing of the organic fractions with brine (100 ml)
12. 12
    Dryingdrying over magnesium sulfate
13. 13
    Filtrationfiltering
14. 14
    Concentrationconcentration under reduced pressure
15. 15
    Otherafforded a brown residue
16. 16
    OtherPurification by column chromatography on silica gel (5 g)
17. 17
    Washeluting in an isocratic fashion with ethyl acetate:hexane (2:1)

Procedure

To a solution of 2-{[5-amino-4-(1,3-benzodioxol-5-yl)-1-methyl-1H-pyrazol-3-yl]oxy}ethyl acetate (Preparation 33) (500 mg) in anhydrous pyridine (5 ml) at room temperature and under an atmosphere of nitrogen was added 4-dimethylaminopyridine (191 mg) and 5-isopropyl-2-pyridinesulfonyl chloride (1.72 g). After being left to reflux overnight, the reaction mixture was poured onto saturated citric acid solution (50 ml) and extracted with ethyl acetate (2×50 ml). The organic fractions were washed with brine (50 ml), followed by drying over magnesium sulfate, filtering and concentration under reduced pressure. To a solution of the residue in ethanol (50 ml) was added sodium hydroxide solution (5 ml of 2M). The mixture was stirred overnight before being concentrated to approximately 5 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 (5 g), eluting in an isocratic fashion with ethyl acetate:hexane (2:1) afforded the title compound as a gum (18 mg).

Source