Br[C:2]1[CH:3]=[C:4]([CH2:8][OH:9])[CH:5]=[N:6][CH:7]=1.[Cl:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C:17](=[O:21])[NH:16][CH2:15][CH2:14]2.C([O-])([O-])=O.[Cs+].[Cs+].N[C@H]1CCCC[C@@H]1N>O1CCOCC1.[Cu]I.O>[Cl:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C:17](=[O:21])[N:16]([C:2]1[CH:7]=[N:6][CH:5]=[C:4]([CH2:8][OH:9])[CH:3]=1)[CH2:15][CH2:14]2In a 25 mL sealed tube, (5-bromo-pyridin-3-yl)-methanol (900 mg, 4.8 mmol), 6-chloro-3,4-dihydro-2H-isoquinolin-1-one (intermediate A-2) (800 mg, 4.4 mmol), CuI (200 mg, 1.1 mmol), Cs2CO3 (3.0 g, 9.2 mmol) and (+)-(S,S)-1,2-diaminocyclohexane (0.4 mL, 3.2 mmol) were dissolved in dioxane (8.0 mL). The resulting reaction mixture was heated at 150° C. for 3 hours before it was poured into H2O (50 mL) and extracted with EtOAc (2×125 mL). The organic layer was washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude product which was purified by silica gel flash chromatography (30-100% EtOAc-hexane gradient) to yield the title compound (1.1 g, 90%) as a light yellow solid. MS: 289.2 (M+H+).
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