Cl[C:2]1[N:7]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[CH2:9])[CH:5]=[C:4]([CH2:13][O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:3]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][C:28]=1[C:29]1[CH:34]=[C:33]([CH3:35])[N:32]=[N:31][CH:30]=1)[NH2:25].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:11]([O:10][C:8]([C:6]1[CH:5]=[C:4]([CH2:13][O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:3]=[C:2]([NH:25][C:24]2[CH:26]=[CH:27][C:28]([C:29]3[CH:34]=[C:33]([CH3:35])[N:32]=[N:31][CH:30]=3)=[C:22]([O:21][CH3:20])[CH:23]=2)[N:7]=1)=[CH2:9])[CH3:12]2-Chloro-4-(1-ethoxyvinyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine (0.70 g, 2.36 mmol), 3-methoxy-4-(6-methylpyridazin-4-yl)aniline (0.508 g, 2.36 mmol), cesium carbonate (1.538 g, 4.72 mmol), palladium(II) acetate (0.079 g, 0.35 mmol) and 2-(dicyclohexylphosphino)biphenyl (0.124 g, 0.35 mmol) were mixed in dioxane (16 mL). The vial was capped, evacuated and flushed with nitrogen. The reaction mixture was heated at 120° C. for 1.5 h. The mixture was filtered and the filter was washed with mixtures of methanol and DCM. The filtrate was concentrated. The residue was purified by column chromatography on silica column eluting with a gradient of methanol and DCM to give the title compound as a solid 702 mg (63%).
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