Water → 4-Nitrophenyl 4-(4-Cyanophenyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,5,6,7,8-hexahydroquinazoline-3(4H)-carboxylate

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Reaction Steps

N,N-Diisopropylethylamine (1.65 mL, 9.72 mmol) and 4-dimethylaminopyridine (59 mg, 0.49 mmol) are added to a solution of 4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-benzonitrile (example 1, 1.00 g, 2.43 mmol) in dichloromethane (6 mL), and the mixture is cooled in an ice bath. A solution of 4-nitrophenyl chloroformate (540 mg, 2.67 mmol) in dichloromethane (2 mL) is added, and the mixture is warmed to room temperature. After 3 h another portion of 4-nitrophenyl chloroformate (980 mg, 4.86 mmol) and N,N-diisopropylethylamine (830 μL, 4.86 mmol) are added, and the mixture is stirred over night. Water is added and the mixture is extracted twice with dichloromethane. The combined organic layers are dried over Na2SO4 and concentrated under reduced pressure. The residue is purified twice by flash chromatography on silica (first purification: gradient cyclohexane/ethyl acetate 100:0 to 70:30, second purification: gradient cyclohexane/ethyl acetate 100:0 to 50:50). Yield: 374 mg; ESI mass spectrum [M+H]+=577, Retention time HPLC: 0.92 min (Z018_S04).

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