Sulfuric Acid → 9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione
Reaction equation
C([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12](CC2C=CC(Cl)=CC=2C2C=CC=C(F)C=2)[N:11]2[CH2:31][CH2:32][N:33]([CH:36]([CH3:38])[CH3:37])[C:34](=[O:35])[C:10]=12)C1C=CC=CC=1.S(=O)(=O)(O)O>C(O)(=O)C>[OH:8][C:9]1[C:14](=[O:15])[N:13]=[CH:12][N:11]2[CH2:31][CH2:32][N:33]([CH:36]([CH3:38])[CH3:37])[C:34](=[O:35])[C:10]=12Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a stirred solution of 9-benzyloxy-6-(5-chloro-3′-fluoro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (383) (60 mg, 0.113 mmol) in acetic acid (1 mL), concentrated sulfuric acid (0.001 mL, 0.023 mmol) was added. The reaction mixture was stirred for 4 h, at room temperature (monitored by LC-MS). Volatiles were removed from the reaction and the residue was quenched with ice cold water (5 mL). Aqueous saturated NaHCO3 was added to adjust the pH to 8. The quenched mass was extracted with ethyl acetate (2×15 mL) and the combined organic part was dried, concentrated and purified by preparative HPLC to get 6-(5-chloro-3% fluoro-biphenyl-2-ylmethyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (384) (20.0 mg, 40.06%) as an off-white solid.