反应详情

To a solution of methyl 4-formyl-2-(trifluoromethyl)benzoate (Intermediate 82) (180 mg, 0.80 mmol), 1,2-diphenyl-ethanone (222 mg, 0.80 mmol) and urea (145 mg, 2.4 mmol) in ethanol (3 mL) was added conc. HCl (0.2 mL), then the resulting mixture was refluxed for 2 days. The mixture was concentrated in vacuo to give methyl 4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)-2-(trifluoromethyl)benzoate, which was used crude. This was taken up in MeOH (3 mL) and 2 N aq. NaOH (3 mL) was added; then the resulting mixture was stirred at 40° C. for 3 hours. The mixture was acidified with aqueous HCl till pH=5 and then followed a standard aqueous/EtOAc workup. Purified by prep-HPLC (0.1% TFA as additive) to give Compound 157 (34 mg, two steps yield 10%) as white solid. 1H NMR (MeOD 400 MHz) δ 7.82 (d, J=8.0 Hz, 1H), 7.72-7.67 (m, 2H), 7.36-7.20 (m, 5H), 7.10-7.05 (m, 3H), 6.88-6.85 (m, 2H), 5.30 (s, 1H). MS (ESI): m/z 439.2 [M+1]+.

1. temperaturethe resulting mixture was refluxed for 2 days
2. concentrationThe mixture was concentrated in vacuo