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

Participants

Reaction Conditions

Reaction Steps

To a mixture of methyl 2-chloro-4-formylbenzoate (Intermediate 75) (210 mg, 1.1 mmol), 1,2-diphenylethanone (208 mg, 1.1 mmol), urea (191 mg, 3.2 mmol) and conc. HCl (0.5 mL) in ethanol (2 mL) was refluxed at 95° C. for 30 hours. A standard aqueous/EtOAc workup procedure was followed to give crude ethyl 2-chloro-4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoate (360 mg). This was taken up in water (2.5 mL) and ethanol (2.5 mL) and sodium hydroxide (67 mg, 1.7 mmol) was added at 30° C. The resulting mixture was stirred at 40° C. for 6 hours. HCl (2 N) was added until pH=3. A standard aqueous/EtOAc workup procedure was followed and crude was purified by prep-HPLC (0.1% TFA as additive) to give Compound 145 (57.3 mg, yield 17%). 1H NMR (DMSO 400 MHz): δ 13.37 (brs, 1H), 8.76 (s, 1H), 7.78 (d, J=7.6 Hz, 1H), 7.63 (s, 1H), 7.43-7.36 (m, 2H), 7.26-7.19 (m, 5H), 7.05-6.98 (m, 3H), 6.81 (d, J=6.4 Hz, 2H), 5.28 (d, J=2.4 Hz, 1H), MS (ESI): m/z 404.9 [M+H]+.

Provenance & Evidence