反应详情

温度

80 °C

To a suspension of (6-bromo-4-((trans-4-((methylamino)methyl)cyclohexyl)amino)quinolin-3-yl)(cyclopropyl)methanone (42 mg, 0.10 mmol), 2,6-dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (43 mg, 0.15 mmol) and Pd(dppf)Cl2 (11 mg, 0.015 mmol) in dioxane (4 mL) was added Cs2CO3 (1.0 M in H2O, 0.4 mL, 0.4 mmol). N2 gas was bubbled through the reaction mixture and the mixture was then heated at 80° C. for 2 h. The solution was allowed to cool to room temperature, diluted with saturated sodium bicarbonate solution and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated. The resultant residue was purified by preparative HPLC (C18 silica, 10-90% methanol/water with 0.05% TFA). The residue was eluted through an ion-exchange column (using methanol and 7 N methanol in ammonia) to obtain the desired product (14.7 mg, 29%) as a yellow solid. 1H NMR (500 MHz, MeOD+TFA-d) δ 9.35 (br s, 1H), 8.47 (br s, 1H), 8.27 (dd, J=8.8, 1.8 Hz, 1H), 7.98 (d, J=8.7 Hz, 1H), 7.74 (s, 2H), 4.52 (br s, 1H), 2.94 (d, J=6.9 Hz, 2H), 2.83 (br s, 2H), 2.73 (s, 3H), 2.46-2.42 (br s, 2H), 2.05 (d, J=13.0 Hz, 2H), 1.88 (br s, 1H), 1.77-1.68 (m, 2H), 1.36-1.19 (m, 6H). ESI MS m/z 498 [C27H29Cl2N3O2+H]+; HPLC>99% (AUC), tR=11.08 min.

1. customN2 gas was bubbled through the reaction mixture
2. temperatureto cool to room temperature
3. additiondiluted with saturated sodium bicarbonate solution
4. extractionextracted with ethyl acetate
5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
6. concentrationconcentrated
7. customThe resultant residue was purified by preparative HPLC (C18 silica, 10-90% methanol/water with 0.05% TFA)
8. washThe residue was eluted through an ion-exchange column (using methanol and 7 N methanol in ammonia)