Phosphorus oxychloride → 1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonamide

Participants

Reaction Steps

To a suspension of (+)-1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonic acid (prepared in Example 196) (2.67 g) in acetonitrile (20 ml) were added pyridine (0.81 ml) and phosphorus oxychloride (1.87 ml) and the resulting mixture was stirred at room temperature for forty five minutes. Without an isolation of the formed 1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonyl chloride, the reaction solution was added dropwise to ammonia water (28%, 20 ml) that cooled to 0° C. and the resulting mixture was stirred for ten minutes. To the reaction solution were added water (40 ml) and ethyl acetate (40 ml×2) such that the intended products were extracted into an organic layer. The organic layer washed with 4% ammonia water (20 ml), saturated saline (8 ml), 1N hydrochloric acid (20 ml×2) and saturated saline (20 ml), dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate) to afford (+)-1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonamide (2.33 g). UPLC/MS 531 (M+H)/0.87 min. (measurement condition 9)

Provenance & Evidence