C([O:5][C:6](=O)[NH:7][CH2:8][CH2:9][N:10]1[CH2:19][CH2:18][C:17]2[C:12](=[CH:13][C:14]([O:22][CH3:23])=[C:15]([O:20][CH3:21])[CH:16]=2)[CH:11]1[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)(C)(C)C.Cl.C1N=CN(C(N2C=NC=C2)=O)C=1.[NH2:46][C:47]1[C:56]2[CH2:55][CH2:54][CH2:53][CH2:52][C:51]=2[N:50]=[CH:49][CH:48]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CC(O)=O.O>[F:31][C:28]1[CH:27]=[CH:26][C:25]([CH2:24][CH:11]2[C:12]3[C:17](=[CH:16][C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=3)[CH2:18][CH2:19][N:10]2[CH2:9][CH2:8][NH:7][C:6]([NH:46][C:47]2[C:56]3[CH2:55][CH2:54][CH2:53][CH2:52][C:51]=3[N:50]=[CH:49][CH:48]=2)=[O:5])=[CH:30][CH:29]=1To a stirred solution of {2-[1-(4-fluoro-benzyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl]-ethyl}-carbamic acid tert-butyl ester (example 106.1, 0.22 g, 0.5 mmol) in glacial AcOH (1 mL) is added conc. HCl (0.1 mL). After 5 min, the reaction mixture is partitioned between CHCl3 (20 mL) and 1 N NaOH (15 mL). The organic phase is evaporated. The residue is taken up in DMSO (2 mL) and treated with CDI (0.2 g, 0.6 mmol, 1.2 eq). The reaction mixture is stirred at rt for 3 h, and then 4-amino-5,6,7,8-tetrahydroquinoline (example C4, 0.19 g, 0.6 mmol) is added. To the resulting solution is added in a single portion NaHMDS (2 M in THF, 1.25 mL, 2.5 mmol). The reaction mixture is stirred at rt for 30 min, then H2O (0.4 mL) is added. The reaction mixture is evaporated and the residue purified by preparative HPLC to provide the title compound.
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