Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([NH2:9])[N:3]=1.[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1B(O)O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(COC)OC>[Cl:8][C:6]1[CH:7]=[C:2]([C:15]2[CH:16]=[C:11]([Cl:10])[CH:12]=[CH:13][C:14]=2[Cl:17])[N:3]=[C:4]([NH2:9])[N:5]=1
To a mixture of 4,6-dichloro-pyrimidin-2-yl-amine (0.625 g, 3.81 mmol), 2,5-dichloro-phenyl boronic acid (0.726 g, 3.81 mmol), palladium (II) acetate (0.128 g, 0.57 mmol) and triphenylphosphine (0.30 g, 1.14 mmol) was added a solution of sodium carbonate (2.0 g, 19.0 mmol) in water (5 ml) followed by glyme (20 ml). The mixture was stirred under an argon atmosphere for 6 hours. Filtration and concentration of the filtrate yielded the crude product which was purified by flash chromatography on silica gel eluting with ethyl acetate-chloroform (1:8). After evaporation of solvents under reduced pressure, the residue was dissolved in ethanol (100 ml) and stirred while a solution of hydrogen chloride in dioxane (4.0 M, 2.5 ml) was added. After evaporation of volatiles under reduced pressure, the residue was treated with ethyl acetate (25 ml) and stirred for 16 hours. Filtration provided the hydrochloride salt of 4-chloro-6-(2,5-dichloro-phenyl)-pyrimidin-2-yl-amine (0.330 g, 28% yield) as a white powder.
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