Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[N:19]=[CH:18][C:17]3[C:16]4[CH2:15][C:14]([CH3:21])([CH3:20])[CH2:13][C:12]=4[S:11][C:10]=3[C:9]2=[O:22])[C:3]=1[CH:23]=[O:24].[CH3:25][O:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][N:32]2[N:35]=[C:36]([NH:38][C:39]3[C:40](=[O:55])[N:41]([CH3:54])[CH:42]=[C:43](B4OC(C)(C)C(C)(C)O4)[CH:44]=3)[CH:37]=[C:31]2[CH2:30]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(#N)C>[CH3:20][C:14]1([CH3:21])[CH2:13][C:12]2[S:11][C:10]3[C:9](=[O:22])[N:8]([C:4]4[C:3]([CH:23]=[O:24])=[C:2]([C:43]5[CH:44]=[C:39]([NH:38][C:36]6[CH:37]=[C:31]7[CH2:30][N:29]([CH2:28][CH2:27][O:26][CH3:25])[CH2:34][CH2:33][N:32]7[N:35]=6)[C:40](=[O:55])[N:41]([CH3:54])[CH:42]=5)[CH:7]=[CH:6][N:5]=4)[N:19]=[CH:18][C:17]=3[C:16]=2[CH2:15]1A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 4-chloro-2-{4,4-dimethyl-9-oxo-7-thia-10,11-diazatricyclo[6.4.0.02,6]dodeca-1(8),2(6),11-trien-10-yl}pyridine-3-carbaldehyde 282i (60 mg, 0.167 mmol), 304d (143.4 mg, 0.334 mmol), Pd(dppf)Cl2 (6.8 mg, 0.0084 mol), K3PO4 (70.8 mg, 0.334 mmol), sodium acetate (27.4 mg, 0.334 mmol), acetonitrile (10 mL), and water (3 drops). The system was subjected to three cycles of vacuum/nitrogen flush and heated at 100° C. for 1 h under N2 protection. Analysis of reaction mixture by LCMS showed complete conversion to the desired product. It was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 40:1 dichloromethane/methanol to afford 304e (80 mg, 77%) as white solid. MS-ESI: [M+H]+ 626.8
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