Acetic Acid → HCID 71513859, compound

Participants

Reaction Steps

To a solution of 3-isopropyl-6-methyl-5-nitro-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione (prepared in Reference Example 195) (1.68 g) in ethyl acetate/methanol (20.0 ml/20.0 ml) was added palladium hydroxide (500.0 mg) and the resulting mixture was performed catalytic hydrogenation at room temperature for four and a half hours. The reaction mixture was degassed and then filtered through Celite (trade mark) and then concentrated under reduced pressure to afford the residue (897.0 mg) containing 5-amino-3-isopropyl-6-methyl-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione. A solution of the resulting residue (150.0 mg), dimethylformamide dimethylacetal (340 μl) and acetic acid (7 μl) in N,N-dimethy formamide (4.0 ml) was stirred at 110° C. for forty-five minutes and then cooled to room temperature, and thereto were added 4-cyanobenzohydrazide (221.4 mg) and acetic acid (690 μl) and the resulting mixture was stirred at 130° C. for two hours. To the reaction mixture was added water (30 ml) and the resulting mixture was extracted with ethyl acetate (30 ml×2). The organic layer was washed with water (30 ml×2) and saturated saline (30 ml), dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: chloroform/methanol) and aminosilica gel column chromatography (eluent: ethyl acetate/methanol) to afford 4-(4-(3-isopropyl-6-methyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-4H-1,2,4-triazol-3-yl)benzonitrile (64.1 mg).

Provenance & Evidence