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

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Reaction Steps

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).

Provenance & Evidence