Hydrochloric Acid → Ethyl 2-nitro-4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoate

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-formyl-2-nitrobenzoic acid (Intermediate 73) (120 mg, 0.615 mmol), 1,2-diphenylethanone (120 mg, 0.615 mmol), urea (110 mg, 1.845 mmol), hydrochloric acid (0.5 mL) in ethanol (2 mL) was heated at 92° C. for 41 hours. A standard aqueous/EtOAc workup was followed to give crude ethyl 2-nitro-4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoate (170 mg, yield 62.3%). This was taken up in water (3 mL) and ethanol (3 mL) and sodium hydroxide (30.6 mg, 0.766 mmol) was added at 0° C., and the mixture was stirred at 28° C. for 5 hours. The reaction mixture was partitioned between water (30 mL) and ethyl acetate (70 mL). The organic layer was discarded and the aqueous layer was adjusted to pH=3 with hydrochloric acid (2 mol/L). Then the resulting mixture was extracted with ethyl acetate (30 mL×3). The organic layers were washed with brine (50 mL), dried over sodium sulfate and evaporated. Purified by preparative HPLC to give Compound 140 (37.1 mg, yield 23.3%). 1HNMR (DMSO-d6 300 MHz): δ 11.38 (s, 1H), 8.82 (s, 1H), 7.84 (d, J=7.8 Hz, 2H), 7.75-7.69 (m, 2H), 7.24 (m, 5H), 7.04-7.01 (m, 3H), 6.83 (d, J=7.8 Hz, 2H), 5.45 (d, J=2.7 Hz, 1H); MS (ESI): m/z 416.0 [M+H]+.

Provenance & Evidence