Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]([CH3:18])([CH3:17])[CH2:15]Cl)[CH:6]=[C:5]2[CH:19]=[O:20].C([O-])(=[O:23])C.[K+].[CH:26]1([NH:29][C:30](=[O:48])[C:31]2[CH:36]=[C:35](B3OC(C)(C)C(C)(C)O3)[C:34]([CH3:46])=[C:33]([F:47])[CH:32]=2)[CH2:28][CH2:27]1.C(=O)([O-])[O-].[K+].[K+]>CN1C(=O)CCC1.O.CO>[CH:26]1([NH:29][C:30](=[O:48])[C:31]2[CH:36]=[C:35]([C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[C:8](=[O:12])[N:7]([CH2:13][C:14]([CH3:18])([CH3:17])[CH2:15][OH:23])[CH:6]=[C:5]4[CH:19]=[O:20])[C:34]([CH3:46])=[C:33]([F:47])[CH:32]=2)[CH2:27][CH2:28]1A solution of 6-bromo-2-(3-chloro-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinoline-4-carbaldehyde (Example 2b, 0.50 g) dissolved in NMP (5 mL) was treated with potassium acetate (0.17 g) under nitrogen. The resulting mixture was stirred at 130° C. for 20 h. The mixture was then treated with N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.63 g), Pd-118 (0.046 g) and potassium carbonate (0.43 g) under nitrogen and stirred at 80° C. for 4 h. After cooling to room temperature methanol (10 mL) was added and the mixture stirred for 1 h. The reaction mixture was diluted with water (250 mL), and extracted with ethyl acetate (250 mL). The organic was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified (SiO2 chromatography, elution with 100% ethyl acetate) to afford the subtitle compound (0.55 g) as an oil.
불러오는 중…