反应详情

温度

100 °C

A mixture of 5-chloro-N-(5-fluoro-6-methoxypyridin-3-yl)-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-amine (151 mg, 0.384 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (36.6 mg, 0.077 mmol, Aldrich, St. Louis, Mo.), palladium diacetate (8.63 mg, 0.038 mmol, Aldrich, St. Louis, Mo.), copper(I) iodide (15 mg, 0.077 mmol, Aldrich, St. Louis, Mo.), cesium fluoride (117 mg, 0.769 mmol, Alfa Aesar) and tributyl(1-ethoxyvinyl)tin (0.195 mL, 0.577 mmol, Aldrich, St. Louis, Mo.) in dioxane (3 mL) was stirred at 100° C. for 18 h. The mixture was cooled down to room temperature. The reaction mixture was diluted with water (10 mL) and extracted with CH2Cl2 (2×30 mL). The combined organic extracts were washed with saturated NaCl (10 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a yellow solid. The crude product was purified by silica gel chromatography, eluting with 10% EtOAc/CH2Cl2 to give 1-(5-(5-fluoro-6-methoxypyridin-3-ylamino)-6-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-yl)ethanone (102 mg, 0.255 mmol, 66.3% yield). 1H NMR (300 MHz, CDCl3) δ 2.66 (s, 3H) 2.71 (s, 3H) 2.81 (s, 3H) 4.05 (s, 3H) 8.04-8.33 (m, 3H) 8.92 (s, 1H) 12.99 (s, 1H). m/z (ESI, +ve ion) 401.0 (M+H)+.

1. temperatureThe mixture was cooled down to room temperature
2. extractionextracted with CH2Cl2 (2×30 mL)
3. washThe combined organic extracts were washed with saturated NaCl (10 mL)
4. dry with materialdried over Na2SO4
5. filtrationThe solution was filtered
6. concentrationconcentrated in vacuo
7. customto give the crude material as a yellow solid
8. customThe crude product was purified by silica gel chromatography
9. washeluting with 10% EtOAc/CH2Cl2