反应详情

温度

100 °C

A mixture of N2-(4-bromo-2-methoxyphenyl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine (0.151 g, 0.4 mmol), Pd(dppf)Cl2 (33 mg, 0.04 mmol) and 1-methyl-5-(tributylstannyl)-1H-imidazole (297 mg, 0.8 mmol) in dioxane (5 mL) was degassed under a stream of nitrogen for 10 min. The reaction tube was sealed and heated at 100° C. during 18 hours. The mixture was cooled and concentrated under reduced pressure. The residue was partitioned between ethyl acetate (20 mL) and water (20 mL) and the product extracted into ethyl acetate (2×20 mL). The combined organics were passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification of the residue via preparative HPLC afforded N2-(2-methoxy-4-(1-methyl-1H-imidazol-5-yl)phenyl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine as a beige solid (64 mg, 42%). LCMS (10 cm_ESCI_Bicarb_MeCN): [MH+]=379 at 3.59 min. 1H NMR (400 MHz, DMSO): δ 8.33 (d, J=8.3, 1H); 8.21 (s, 1H); 8.10 (s, 1H); 7.72 (s, 1H); 7.23 (d, J=5.2, 1H); 7.16-7.07 (m, 3H); 3.95 (s, 3H); 3.74 (s, 3H); 2.96 (d, J=4.3, 3H).

1. customwas degassed under a stream of nitrogen for 10 min
2. customThe reaction tube was sealed
3. temperatureThe mixture was cooled
4. concentrationconcentrated under reduced pressure
5. customThe residue was partitioned between ethyl acetate (20 mL) and water (20 mL)
6. extractionthe product extracted into ethyl acetate (2×20 mL)
7. customThe combined organics were passed through a phase separation cartridge
8. customthe solvent removed under reduced pressure
9. customPurification of the residue via preparative HPLC