I[C:2]1[C:3]([NH:10][CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[N:4][C:5]([NH2:9])=[N:6][C:7]=1[CH3:8].C(N(CC)CC)C.[C:24]([O:28][CH2:29][CH3:30])(=[O:27])[CH:25]=[CH2:26]>CN(C=O)C>[NH2:9][C:5]1[N:6]=[C:7]([CH3:8])[C:2](/[CH:26]=[CH:25]/[C:24]([O:28][CH2:29][CH3:30])=[O:27])=[C:3]([NH:10][CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[N:4]=1To a solution of 5-iodo-6-methyl-N4-(tetrahydro-2H-pyran-4-yl)pyrimidine-2,4-diamine (10.0 g, 30.0 mmol) in DMF (200 mL) was added triethylamine (12.50 mL, 90.0 mmol) and ethyl acrylate (9.80 mL, 90.0 mmol) successively at room temperature. The reaction was purged with nitrogen for 5 min. and Pd(PPh3)4 (10 mol %, 3.50 g) was added. The reaction was heated to 95° C., stirred for overnight under nitrogen, and then cooled to room temperature. Nearly all DMF was evaporated under reduced pressure. The reaction was poured into ethyl acetate (500 mL) and H2O (300 mL). The organic layer collected and dried over anhydrous sodium sulfate, and concentrated in vacuo to afford the crude product. The product was purified by a flash chromatography (70% ethyl acetate/hexanes to 10% EtOH/ethyl acetate) to afford (E)-ethyl 3-(2-amino-4-methyl-6-(tetrahydro-2H-pyran-4-ylamino)pyrimidin-5-yl)acrylate, as a light yellow semicrystal (yield: 6.85 g, 75.0%). LC/MS: calculated for C15H22N4O3 (306.17). found: 307.2 (MH+). HPLC analytical purity: >97.0%.
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