反应详情

To a stirred solution of 9-benzyloxy-2-cyclopropyl-6-(1-pyridin-2-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (452) (250 mg, crude) in acetic acid (4 mL), concentrated H2SO4 (0.001 mL) was added and the reaction mixture was stirred for 2 h at room temperature (monitored by LC-MS). Volatiles were removed from the reaction mixture ant the residue was quenched with ice water (10 mL). The pH of the mixture was adjusted to 8 using NaHCO3 and extracted with 10% methanol in dichloromethane (2×40 mL). The crude product obtained after drying and concentrating the organic part was purified by preparative HPLC to get 2-cyclopropyl-9-hydroxy-6-(1-pyridin-2-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (453) (17.3 mg, 30% 2 steps) as an off-white solid.

1. customVolatiles were removed from the reaction mixture ant the residue
2. customwas quenched with ice water (10 mL)
3. extractionextracted with 10% methanol in dichloromethane (2×40 mL)
4. customThe crude product obtained
5. customafter drying
6. concentrationconcentrating the organic part
7. customwas purified by preparative HPLC