反应详情

To a stirred solution of 9-benzyloxy-6-(5,4′-dichloro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (10a) (35 mg, 0.064 mmol) in acetic acid (1 mL), concentrated H2SO4 (0.001 mL, 0.013 mmol) was added and the reaction mixture was stirred for 4 h at room temperature (reaction was monitored by LC/MS). Volatiles were removed from the reaction mixture and the residue was quenched with ice cold water (5 mL). The pH of this mixture was adjusted to pH 8 using NaHCO3. After extraction with ethyl acetate (2×15 mL), the organic part was dried and concentrated. The resulting crude product was purified by prep HPLC to get 6-(5,4′-dichloro-biphenyl-2-ylmethyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (P046-03-EB-01) (18.1 mg, 61.72%) as an off-white solid.

1. custom(reaction was monitored by LC/MS)
2. customVolatiles were removed from the reaction mixture
3. customthe residue was quenched with ice cold water (5 mL)
4. extractionAfter extraction with ethyl acetate (2×15 mL)
5. customthe organic part was dried
6. concentrationconcentrated
7. customThe resulting crude product was purified by prep HPLC