C([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=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.OS(O)(=O)=O>C(O)(=O)C>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][C:12]2[N:11]3[CH2:31][CH2:32][N:33]([CH:36]([CH3:38])[CH3:37])[C:34]([OH:35])=[C:10]3[C:9]([OH:8])=[C:14]([OH:15])[N:13]=2)=[C:18]([C:24]2[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=2)[CH:19]=1To a stirred solution of 9-benzyloxy-6-(5-chloro-4′-fluoro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (385) (30 mg, 0.056 mmol) in acetic acid (1 mL), concentrated H2SO4 (0.001 mL, 0.011 mmol) was added and the reaction mixture was stirred for 4 h at room temperature (monitored by LC-MS). From the reaction, volatiles was removed and the residue was quenched with ice cold water (5 mL). Aqueous saturated NaHCO3 was added to adjust the pH up to 8. The quenched mass was extracted with ethyl acetate (2×15 mL). The combined organic part was dried, concentrated and purified by preparative HPLC to get 6-(5-chloro-4′-fluoro-biphenyl-2-ylmethyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-diol (386) (11.2 mg, 44.86 mmol) as an off-white solid.
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