反应详情

温度

100 °C

A mixture of 2-bromo-5-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidin-4-amine (250 mg, 0.795 mmol), N-(2-methoxyethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-sulfonamide (359 mg, 1.034 mmol, 1.3 eq), Pd(dppf)Cl2 (65 mg, 0.0795 mmol, 0.1 eq) and Na2CO3 (295 mg, 2.783 mmol, 3.5 eq) in 1,4-dioxane (5 mL) and water (1 mL) was stirred at 100° C. under a nitrogen atmosphere for 15 h. The reaction mixture was allowed to cool to room temperature and concentrated to give a residue. The residue was purified by silica gel chromatography (CH2Cl2/methanol 500:1 to 50:1 as eluent) to afford title compound 5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)-N-(2-methoxyethyl) thiophene-2-sulfonamide (Compound 88) (71.2 mg, 28.1%) as solid. LC-MS (m/z)=455.0 [M+H]+; 1H NMR (400 MHz, DMSO-d6): δ 0.75 (d, J=3.6 Hz, 2H), 0.99 (d, J=6.4 Hz, 2H), 1.94 (s, 1H), 3.04 (t, J=5.2 Hz, 2H), 3.20 (s, 3H), 3.37 (t, J=5.0 Hz, 2H), 6.39 (s, 1H), 7.61 (d, J=3.2 Hz, 1H), 7.77 (d, J=3.6 Hz, 1H), 8.15 (s, 1H), 8.46 (s, 1H), 9.49 (s, 1H), 12.35 (s, 1H).

1. temperatureto cool to room temperature
2. concentrationconcentrated
3. customto give a residue
4. customThe residue was purified by silica gel chromatography (CH2Cl2/methanol 500:1 to 50:1 as eluent)