反应详情

温度

110 °C

1,4-Dioxane (40 mL) and water (9 mL) were added to a flask containing 4-(difluoromethyl)-N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine (3.00 g, 8.31 mmol), tert-butyl (2-(4-chloro-1H-pyrazol-1-yl)ethyl)carbamate (3.06 g, 12.5 mmol), SiliaCat Si-DPP-Pd (9.58 g, 2.49 mmol, 0.26 mmol/g), and sodium carbonate (4.40 g, 41.5 mmol). The reaction was heated at 110° C. overnight. The reaction mixture was filtered, washed with 1,4-dioxane, and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (0-100% ethyl acetate/hexanes) and dissolved in a small amount of 1,4-dioxane. Hydrochloric acid (4N in 1,4-dioxane, 10 mL) in was added and the mixture was allowed to stir for 3 hours. The mixture was diluted with diethyl ether, filtered, washed with diethyl ether, and dried over anhydrous sodium sulfate to afford N-(3-(1-(2-aminoethyl)-1H-pyrazol-4-yl)-5-methylphenyl)-4-(difluoromethyl)pyrimidin-2-amine hydrochloride. MS ESI calc'd. for C17H19F2N6 [M+H]+ 345. found 345. 1H NMR (500 MHz, DMSO-d6): δ 9.92 (s, 1H), 8.68 (d, J=4.9 Hz, 1H), 8.29 (s, 3H), 8.15 (s, 1H), 7.87 (s, 1H), 7.85 (s, 1H), 7.34 (s, 1H), 7.04 (t, J=5.3 Hz, 2H), 6.89 (t, J=54.5 Hz, 1H), 4.42 (t, J=6.3 Hz, 2H), 3.27-3.25 (m, 2H), 2.28 (s, 3H).

1. filtrationThe reaction mixture was filtered
2. washwashed with 1,4-dioxane
3. concentrationconcentrated under reduced pressure
4. customThe residue was purified by column chromatography on silica gel (0-100% ethyl acetate/hexanes)
5. dissolutiondissolved in a small amount of 1,4-dioxane
6. additionHydrochloric acid (4N in 1,4-dioxane, 10 mL) in was added
7. additionThe mixture was diluted with diethyl ether
8. filtrationfiltered
9. washwashed with diethyl ether
10. dry with materialdried over anhydrous sodium sulfate