Br[CH2:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7](Cl)=[CH:8][C:9]([C:13]#[N:14])=[N:10]2)=[CH:5][CH:4]=1.[CH:16]1([C:19]2[N:24]=[CH:23][C:22](B3OC(C)(C)C(C)(C)O3)=[CH:21][N:20]=2)[CH2:18][CH2:17]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:42][N:43]1[CH:47]=[C:46](B2OC(C)(C)C(C)(C)O2)[CH:45]=[N:44]1>O1CCOCC1.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(Cl)Cl>[CH:16]1([C:19]2[N:20]=[CH:21][C:22]([CH2:2][C:3]3[CH:12]=[C:11]4[C:6]([C:7]([C:46]5[CH:45]=[N:44][N:43]([CH3:42])[CH:47]=5)=[CH:8][C:9]([C:13]#[N:14])=[N:10]4)=[CH:5][CH:4]=3)=[CH:23][N:24]=2)[CH2:17][CH2:18]1After degassing with N2, a mixture of 7-(bromomethyl)-4-chloroquinoline-2-carbonitrile (2-4, 650 mg, 2.31 mmol), 2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (580 mg, 2.36 mmol), Pd(dppf)Cl2—CH2Cl2 adduct (94 mg, 0.11 mmol), and K3PO4 (1960 mg, 9.24 mmol) in 1,4-dioxane (13.7 mL) and H2O (1.7 mL) was heated at 100° C. for 30 min under microwave condition. The mixture was cooled to room temperature, and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (528 mg, 2.54 mmol) was added. After degassing with N2, the mixture was then heated at 115° C. for 30 min under microwave condition. The reaction mixture was cooled, diluted with H2O (10 mL) and the mixture was extracted with ethyl acetate (2×50 mL). The combined organic fractions were washed with brine, dried (Na2SO4), filtered and the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel, eluting with EtOAc/Hexane (0-100%) to afford 7-((2-cyclopropylpyrimidin-5-yl)methyl)-4-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carbonitrile (6-1, 649 mg, 77%). LRMS m/z (M+H)+ 367.3 found, 367.2 required.
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