[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH2:12][C:13]([F:16])([F:15])[F:14])=[C:6](B(O)O)[CH:7]=1.[Cl:17][C:18]1[CH:23]=[C:22](Cl)[N:21]=[C:20]([NH2:25])[N:19]=1.CC(O)C(O)C.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:17][C:18]1[CH:23]=[C:22]([C:6]2[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[O:11][CH2:12][C:13]([F:16])([F:15])[F:14])[N:21]=[C:20]([NH2:25])[N:19]=1To a mixture of 5-chloro-2-(2,2,2-trifluoro-ethoxy)-phenylboronic acid (1.6 g, 6.3 mmol), 4,6-dichloro-pyrimidin-2-ylamine (1.2 g, 7.6 mmol), palladium acetate (211 mg, 0.95 mmol), and dimethyl ethylene glycol (100 ml), degassed with argon, was added a solution of sodium carbonate (4.0 g, 37.8 mmol) in water (15 ml) followed by triphenylphosphine (495 mg, 1.9 mmol). After stirring for 12 hours, the mixture was filtered through a pad of celite under suction. The organic layer was separated from the filtrate and dried over magnesium sulfate. The mixture was purified by flash chromatography on silica gel eluting with ethyl acetate-hexane (1:5 followed by 1:4) to give 4-chloro-6-[5-chloro-2-(2,2,2-trifluoro-ethoxy)-phenyl]-pyrimidin-2-ylamine, which was dissolved in ethyl acetate (10 ml) and treated with a solution of hydrogen chloride in dioxane (4 M, 2.5 ml). The solid was filtered to provide the hydrochloride salt of 4-chloro-6-[5-chloro-2-(2,2,2-trifluoro-ethoxy)-phenyl]-pyrimidin-2-ylamine (500 mg, 20% yield). 1H NMR (CD3OD) δ 4.78 (q, 2H, J=8.5 Hz, CH2), 7.31-7.33 (m, 2H, Ar), 7.65 (dd, 1H, J=8.9 Hz, J=2.8 Hz, Ar), 7.82 (d, 1H, J=2.6 Hz, Ar).
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