Cl[C:2]1[CH:7]=[C:6](Cl)[N:5]=[C:4]([NH:9][CH3:10])[N:3]=1.[CH3:11][C@@H:12]1[CH2:16][CH2:15][CH2:14][NH:13]1.C([O-])(O)=O.[Na+].ClC1C=C(Cl)N=C(N)N=1.[C:31]([C:33]1[C:38]([F:39])=[CH:37][C:36](B(O)O)=[CH:35][C:34]=1[F:43])#[N:32]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(C)=O>[F:39][C:38]1[CH:37]=[C:36]([C:2]2[CH:7]=[C:6]([N:13]3[CH2:14][CH2:15][CH2:16][C@H:12]3[CH3:11])[N:5]=[C:4]([NH:9][CH3:10])[N:3]=2)[CH:35]=[C:34]([F:43])[C:33]=1[C:31]#[N:32]A mixture of 4,6-dichloro-N-methyl-2-pyrimidinamine (1.2 g, 6.74 mmol), (2R)-2-methylpyrrolidine (0.631 g, 7.41 mmol), and NaHCO3 (2.83 g, 33.7 mmol) in dioxane (40 mL) and water (20 mL) was stirred overnight at 117° C. in a sealed tube. The reaction was allowed to cool to room temperature. LCMS showed most of the starting material 4,6-dichloro-2-pyrimidinamine had been consumed. Then (4-cyano-3,5-difluorophenyl)boronic acid (1.233 g, 6.74 mmol) and Pd(Ph3P)4 (0.156 g, 0.135 mmol) were added, and the reaction mixture was stirred for 24 hours at 117° C. The mixture was poured into water (30 mL) and EtOAc (100 mL). The compound stayed in the EtOAc layer. The organic layer was separated from the aqueous layer. There was some black colored suspension in the organic layer, which was filtered out. (they were not product). The organic layer was rotavaped to dryness to afford the title compound (0.8 g) as a light yellow solid. LC-MS (ES) m/z=330 [M+H]+.
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