反应详情

温度

120 °C

A mixture of 4-(6-chloro-5-methoxy-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (570 mg, 1.73 mmol), 6-methanesulfonyl-4-methyl-pyridin-3-ylamine (272 mg, 1.46 mmol), palladium acetate (27.3 mg, 0.122 mmol), 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (87 μl, 0.245 mmol), and sodium 2-methylpropan-2-olate (249 mg, 2.59 mmol) in 4.5 mL dioxane was heated under microwave irradiation at 120° C. After 4 h, mixture was purified by HPLC; fractions containing pure product were collected and concentrated. Residue was treated with 4M HCl in dioxane, concentrated, and dried under high vacuum to give 4-[6-(6-methanesulfonyl-4-methyl-pyridin-3-ylamino)-5-methoxy-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester as a white solid (HCl salt, 261 mg, 29%). 1HNMR (MeOH-d4, 400 MHz) δ 1.23-1.24 (d, J=6.2 Hz, 6H), 1.75-1.81 (m, 2H), 1.97-2.04 (m, 2H), 2.40 (s, 3H), 3.17 (s, 3H), 3.39-3.46 (m, 2H), 3.71-3.77 (m, 2H), 3.92 (s, 3H), 4.82-4.88 (m, 1H), 5.35-5.40 (m, 1H), 7.99 (s, 1H), 7.99 (s, 1H), 8.96 (s, 1H). Exact mass calculated for C21H29N5O6S 479.18 found 480.4 (MH+).

1. custommixture was purified by HPLC
2. additionfractions containing pure product
3. customwere collected
4. concentrationconcentrated
5. additionResidue was treated with 4M HCl in dioxane
6. concentrationconcentrated
7. customdried under high vacuum