反应详情

温度

75 °C

To a solution of isopropyl 4-(6-chloro-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxylate (0.3 g, 0.91 mmol) in dioxane (3 mL), were added 5-amino-4-methylpicolinonitrile (0.12 g, 0.91 mmol), 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (0.031 g, 0.091 mmol), Pd(OAc)2 (0.10 g, 0.45 mmol), and NaO-t-Bu (0.21 g, 2.2 mmol) at an ambient temperature. The reaction was warmed to 75° C. and stirred for 2 hrs. After cooling to room temperature, the reaction was poured into H2O and extracted with ethyl acetate. The organic layer was dried over MgSO4 and concentrated under vacuum. The residue was purified over SiO2 to afford isopropyl 4-(6-(6-cyano-4-methylpyridin-3-ylamino)-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxylate in 31% (102 mg). 1HNMR (CDCl3, 400 MHz) δ 1.21 (d, J=4.71, 6H), 1.71-1.75 (m, 2H), 1.95-2.01 (m, 2H), 2.31 (s, 3H), 2.62 (s, 3H), 3.32-3.41 (m, 2H), 3.64-3.71 (m, 2H), 4.85-4.90 (m, 1H), 5.35˜5.41 (m, 1H), 7.81 (s, 1H), 8.10 (s, 1H), 8.82 (d, J=4.71 Hz, 1H). Exact mass calculated for C21H26N6O4 426.47. found 427.51 (MH+).

1. temperatureAfter cooling to room temperature
2. extractionextracted with ethyl acetate
3. dry with materialThe organic layer was dried over MgSO4
4. concentrationconcentrated under vacuum
5. customThe residue was purified over SiO2