反应详情

温度

95 °C

A mixture of N-((5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)carbamoyl)isobutyramide (0.136 g, 0.390 mmol), K2CO3 (0.108 g, 0.780 mmol) and 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)morpholine (0.136 g, 0.468 mmol) in dioxane (8 mL) and water (2 mL) was sparged with Ar, treated with Pd(PPh3)4 (0.045 g, 0.039 mmol), sparged again with Ar and heated at 95° C. overnight. The mixture was cooled to RT, treated with EtOAc and the solids removed via filtration through a pad of diatomaceous earth and Na2SO4. The filtrate was concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The material was purified twice more via silica gel chromatography (MeOH/EtOAc). The resulting material was treated with Et2O, sonicated and the solid collected via filtration to afford N-((6-methyl-5-((2′-morpholino-[2,4′-bipyridin]-4-yl)oxy)pyridin-2-yl)carbamoyl)isobutyramide (52 mg, 28%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.05 (s, 1H), 10.84 (s, 1H), 8.54 (d, J=5.6 Hz, 1H), 8.21 (d, J=5.2 Hz, 1H), 7.92 (d, J=8.8 Hz, 1H), 7.73 (d, J=2.4 Hz, 1H), 7.65 (d, J=8.8 Hz, 1H), 7.44 (s, 1H), 7.30 (dd, J=5.2, 1.3 Hz, 1H), 6.80 (dd, J=5.6, 2.4 Hz, 1H), 3.70 (m, 4H), 3.51 (m, 4H), 2.66 (m, 1H), 2.27 (s, 3H), 1.09 (d, J=6.8 Hz, 6H); MS (ESI) m/z: 477.3 (M+H+).

1. customwas sparged with Ar
2. customsparged again with Ar
3. temperatureThe mixture was cooled to RT
4. additiontreated with EtOAc
5. customthe solids removed via filtration through a pad of diatomaceous earth and Na2SO4
6. concentrationThe filtrate was concentrated to dryness
7. custompurified via silica gel chromatography (MeOH/DCM)
8. customThe material was purified twice more via silica gel chromatography (MeOH/EtOAc)
9. additionThe resulting material was treated with Et2O
10. customsonicated
11. filtrationthe solid collected via filtration