[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][C:18]=2[Cl:19])[C:15](=[O:20])[NH:14][CH:13]=[CH:12]3)[CH2:4][CH2:3]1.[CH2:21]([O:23][C:24](=[O:27])[CH:25]=O)[CH3:22].C([BH3-])#N.[Na+]>CO>[CH2:21]([O:23][C:24](=[O:27])[CH2:25][NH:1][C@H:2]1[CH2:3][CH2:4][C@@H:5]([O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][C:18]=2[Cl:19])[C:15](=[O:20])[NH:14][CH:13]=[CH:12]3)[CH2:6][CH2:7]1)[CH3:22]300 mg (0.91 mmol) of 6-cis-(4-amino-cyclohexyloxy)-7-chloro-2H-isoquinolin-1-one (12) were dissolved in 20 ml of methanol and treated with 258 mg (1.14 mmol) glyoxylic acid ethyl ester following the general method for reductive amination reactions. To achieve complete conversion, additional 5.0 equivalents of glyoxylic acid ethyl ester and 0.5 equivalents sodium cyano borohydride were added portionwise over 34 h and the temperature was increased to 60° C. after 5 h reaction time until the reaction went to completion. After filtration, the reaction solution was evaporated. The residue was dissolved in dichloromethane, washed with 1 N NaOH and saturated NaCl-solution, dried over MgSO4 and evaporated. The so obtained crude product was used in the next reaction without further purification. Rt=0.81 min (Method C). Detected mass: 365.4 (M+H+, methyl ester, because methanol was used as solvent), 0.87 min. (Method C). Detected mass: 379.4 (M+H+, ethyl ester, title compound).
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