Cl.[Cl:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][NH:9][C:10]2=[O:13])=[CH:5][C:4]=1[O:14][CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.C(N(CC)CC)C.C(O)(=O)C.[CH3:32][C:33]([CH3:35])=O.C([BH3-])#N.[Na+]>CO>[Cl:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][NH:9][C:10]2=[O:13])=[CH:5][C:4]=1[O:14][CH:15]1[CH2:20][CH2:19][N:18]([CH:33]([CH3:35])[CH3:32])[CH2:17][CH2:16]164 mg (0.23 mmol) of 7-chloro-6-(piperidin-4-yloxy)-2H-isoquinolin-1-one-hydro-chloride (54) were dissolved in 5 mL of methanol. 41.4 mg (0.41 mmol) of triethyl amine were added and the mixture stirred at room temperature for 10 minutes. After adding freshly dried molecular sieves, 122.4 mg (2.04 mmol) acetic acid, 26.7 mg (0.46 mmol) of acetone and 43.3 mg (0.69 mmol) of sodium cyanoborohydride, the reaction mixture was refluxed for 8 h. After the addition of 2 equivalents acetone and 2 equivalents of sodium cyanoborohydride at room temperature, the reaction was refluxed for another 2 h to complete conversion. For working up, the mixture was filtered and the filtrate was evaporated. The residue was dissolved in dichloromethane, washed twice with 2 N NaOH and water and dried over MgSO4. After evaporation of the solvent and purification by preparative HPLC, 13 mg of the title compound were obtained as trifluoroacetate. Rt=0.96 min (Method B). Detected mass: 321.1/323.2 (M+H+).
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