反应详情

温度

140 °C

A glass microwave reaction vessel was charged with 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.150 g, 0.422 mmol, prepared as in Example 2, Step 1-2) and 4-chloro-1-(2-iodo-3-methylphenyl)-3-methyl-1H-pyrazole (0.281 g, 0.845 mmol) in dioxane (3 mL) and 2 M aqueous sodium carbonate (1.0 mL, 2.0 mmol). The vessel was capped with a septum and the solution was degassed by bubbling nitrogen gas through the solution for 10 min. Next, Pd (PPh3)4 (0.049 g, 0.042 mmol) was added and the vessel was sealed. The reaction mixture was stirred and heated in a microwave reactor at 140° C. for 15 min. The reaction was poured into water and the mixture was extracted with EtOAc. The combined organic extracts were washed with water, saturated sodium chloride, and dried over sodium sulfate. The solution was filtered and concentrated in vacuo to give the crude material. The crude material was purified by reverse-phase preparative HPLC with 0.1% TFA in CH3CN/H2O, gradient 5-70% over 20 min to provide 6-(2-(4-chloro-3-methyl-1H-pyrazol-1-yl)-6-methylphenyl)-3-morpholinoquinolin-2-amine as a white solid. The purified compound was portioned between DCM and saturated sodium bicarbonate. The layers were separated and the aqueous layer was extracted with DCM. The combined organic extracts were washed with saturated sodium chloride and dried over sodium sulfate. The solution was filtered and concentrated in vacuo to give 6-(2-(4-chloro-3-methyl-1H-pyrazol-1-yl)-6-methylphenyl)-3-morpholinoquinolin-2-amine as a white solid. MS (ESI, pos. ion) m/z: 434 (M+1).

1. customA glass microwave reaction vessel
2. customThe vessel was capped with a septum
3. customthe solution was degassed
4. customby bubbling nitrogen gas through the solution for 10 min
5. customthe vessel was sealed
6. extractionthe mixture was extracted with EtOAc
7. washThe combined organic extracts were washed with water, saturated sodium chloride
8. dry with materialdried over sodium sulfate
9. filtrationThe solution was filtered
10. concentrationconcentrated in vacuo
11. customto give the crude material
12. customThe crude material was purified by reverse-phase preparative HPLC with 0.1% TFA in CH3CN/H2O, gradient 5-70% over 20 min