反应详情

温度

90 °C

N-(2-chloro-5-morpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)-quinolin-4-amine (49.1 mg, 0.10 mmol), 2-(3-(difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (56.9 mg, 0.21 mmol), tricyclohexylphosphine (5.1 mg, 0.018 mmol), and tris(dibenzylideneacetone)dipalladium (0) (8.9 mg, 9.7 μmol) were added to a flask then degassed and backfilled with argon. To the flask, 1,4-dioxane (2.0 mL) and aq. 1.3M potassium phosphate tribasic (0.21 mL, 0.27 mmol) were added by syringe. The resulting reaction was heated to 90° C. and monitored with TLC and LC-MS. After 19 h, the reaction was cooled to rt then poured into water. After extracting twice with EtOAc and twice with DCM, the combined organic extractions were dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on silica gel (0-45% of a premixed solution of 89:9:1 DCM:MeOH:ammonium hydroxide in DCM) to afford a film that was triturated with MeOH to afford a yellow solid as N-(2-(3-(difluoromethoxy)phenyl)-5-morpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.69 (1H, d, J=4.9 Hz), 8.06 (2H, m), 7.91 (1H, d, J=3.7 Hz), 7.80 (1H, d, J=7.8 Hz), 7.59 (2H, m), 7.47 (2H, m), 7.36 (4H, m), 6.54 (1H, d, J=2.4 Hz), 3.76 (4H, m), 3.15 (4H, m), 2.14 (3H, s). Mass Spectrum (pos.) m/e: 576.1 (M+1).

1. customthen degassed
2. customThe resulting reaction
3. temperaturethe reaction was cooled to rt
4. extractionAfter extracting twice with EtOAc and twice with DCM
5. extractionthe combined organic extractions
6. dry with materialwere dried over anhydrous magnesium sulfate
7. filtrationAfter filtration and concentration
8. customthe residue was purified on silica gel (0-45% of a premixed solution of 89:9:1 DCM:MeOH:ammonium hydroxide in DCM)
9. customto afford a film that
10. customwas triturated with MeOH