Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][OH:17])[CH2:11][CH2:10]2)[CH:3]=1.[NH2:18][C:19]1[S:20][C:21]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][N:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.Cl>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[OH:17][CH2:16][CH2:15][N:12]1[CH2:13][CH2:14][N:9]([C:4]2[N:5]=[C:6]([CH3:8])[N:7]=[C:2]([NH:18][C:19]3[S:20][C:21]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][N:23]=3)[CH:3]=2)[CH2:10][CH2:11]12-(4-(6-chloro-2-methylpyrimidin-4-yl)piperazin-1-yl)ethanol (Compound 4) (25.7 g, 0.1 mol), methyl 2-aminothiazole-5-formate (Compound 5) (18.9 g, 0.12 mol), cesium carbonate (45.6 g, 0.14 mol), palladium acetate (2.2 g, 0.01 mol) and BINAP (6.2 g, 0.01 mol) were mixed with toluene (1100 mL) in reaction flask, and heated by stirring to reflux for 16 h. The reactant was cooled and 2 mol/L hydrochloric acid was added and stirred for 10 mins. After vacuum filtration the filtrate was phase-separated and the aqueous phase was extracted by toluene (500 mL). The separated aqueous phase was neutralized by NaOH solution (6 mol/L) at 10-15° C., and then grew the grains for 1 h. After vacuum filtration the cake was rinsed by water to give yellow solid target Compound 6 (28.5 g, yield: 75.2%).
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