反应详情

温度

100 °C

A mixture of 2-(4-methoxyphenyl)-5-morpholinopyridin-3-amine (60.3 mg, 0.21 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (52.0 mg, 0.17 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl, (X-Phos) (14.7 mg, 0.031 mmol), tris(dibenzylideneacetone)dipalladium (0) (6.8 mg, 7.43 μmol), and sodium tert-butoxide (42.9 mg, 0.45 mmol) in dry toluene (1.5 mL) was degassed by nitrogen. The resulting reaction was heated to 100° 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 basic alumina (10-40% EtOAc in hexanes) to afford a >80% pure light yellow film that was triturated with isopropanol to afford a light yellow solid as 5,7-difluoro-N-(2-(4-methoxyphenyl)-5-morpholinopyridin-3-yl)-3-methyl-2-(4-methylpyridin-2-yl)-quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.54 (1H, d, J=5.1 Hz), 8.00 (1H, d, J=2.3 Hz), 7.81 (4H, m), 7.61 (1H, d, J=9.6 Hz), 7.20 (1H, d, J=4.7 Hz), 7.10 (4H, m), 6.53 (1H, d, J=2.3 Hz), 3.99 (7H, m), 3.26 (4H, m), 2.48 (3H, s), 2.21 (3H, s). Mass Spectrum (pos.) m/e: 554.2 (M+1).

1. customwas degassed by nitrogen
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 basic alumina (10-40% EtOAc in hexanes)
9. customto afford a >80% pure light yellow film that
10. customwas triturated with isopropanol