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 (0.128 g, 0.361 mmol, prepared as in Example 2, Step 1-2), potassium phosphate (0.306 g, 1.443 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.034 g, 0.072 mmol), Pd2db3 (0.017 g, 0.018 mmol), and 1-(2-bromophenyl)-4,5,6,7-tetrahydro-1H-indazole (0.200 g, 0.722 mmol). The vessel was evacuated and flushed with N2 3× before dioxane (2.4 mL) and water (1.2 mL) (each degassed by bubbling N2 gas through the solution for 10 min prior to addition) were added. The reaction mixture was stirred and heated in a microwave reactor at 140° C. for 15 min. The reaction mixture was diluted with 10:1 saturated ammonium chloride/ammonium hydroxide and extracted with EtOAc. The combined organic extracts were washed with 10:1 saturated ammonium chloride/ammonium hydroxide, 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 silica gel chromatography by eluting through a plug of silica with 1:1 EtOAc/Hexanes then 1:10 2M NH3 in MeOH/DCM. The sample was further purified by reverse-phase preparative HPLC with 0.1% TFA in CH3CN/H2O, gradient 5-20% over 15 min to provide 3-morpholino-6-(2-(4,5,6,7-tetrahydro-1H-indazol-1-yl)phenyl)quinolin-2-amine. The purified compound was partitioned between DCM and saturated sodium bicarbonate. The layers were separated and the aqueous layer was extracted with dichloromethane. 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 the pure material as a white solid. MS (ESI, pos. ion) m/z: 426 (M+1).

1. customA glass microwave reaction vessel
2. customThe vessel was evacuated
3. customflushed with N2 3× before dioxane (2.4 mL) and water (1.2 mL) (
4. customeach degassed
5. customby bubbling N2 gas through the solution for 10 min
6. additionto addition)
7. additionwere added
8. additionThe reaction mixture was diluted with 10:1 saturated ammonium chloride/ammonium hydroxide
9. extractionextracted with EtOAc
10. washThe combined organic extracts were washed with 10:1 saturated ammonium chloride/ammonium hydroxide, water, saturated sodium chloride
11. dry with materialdried over sodium sulfate
12. filtrationThe solution was filtered
13. concentrationconcentrated in vacuo
14. customto give the crude material
15. customThe crude material was purified by silica gel chromatography
16. washby eluting through a plug of silica with 1:1 EtOAc/Hexanes
17. customThe sample was further purified by reverse-phase preparative HPLC with 0.1% TFA in CH3CN/H2O, gradient 5-20% over 15 min