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

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 4-formyl-2-hydroxybenzoate (Intermediate 84) (125 mg, 0.69 mmol), 1,2-diphenylethanone (136.2 mg, 0.69 mmol), urea (124.8 mg, 2.08 mmol), concentrated hydrochloric acid (1.0 mL) in ethanol (5 mL) was heated at 90° C. for 40 hours. Followed standard aqueous/EtOAc workup procedure to give crude ethyl 2-hydroxy-4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoate (200 mg, yield 69.5%). To a solution of this crude material (200 mg, 0.483 mmol) in water (5 mL) and ethanol (5 mL) was added sodium hydroxide (38.64 mg, 0.966 mmol) at 0° C. The mixture was stirred at 30° C. for 4 hours, then partitioned between ethyl acetate (70 mL) and water (50 mL). The organic layer was discarded and the aqueous layer was adjusted to pH=3 by hydrochloric acid (2M). Followed a standard aqueous/EtOAc workup. The residue was purified by preparative HPLC to give Compound 138 (31.3 mg, yield 16.8%). 1HNMR (DMSO-d6 400 MHz): δ 11.27 (s, 1H), 8.71 (s, 1H), 7.77 (d, J=8.0 Hz, 1H), 7.26 (s, 1H), 7.25-7.19 (m, 5H), 7.03-6.99 (m, 3H), 6.93 (d, J=8.0 Hz, 1H), 6.87 (s, 1H), 6.81 (d, J=6.4 Hz, 2H), 5.16 (d, J=2.8 Hz, 1H); MS (ESI): m/z 387.0 [M+H]+.

Provenance & Evidence