反应详情

温度

95 °C

A mixture of N-((5-((2-chloropyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydro-2H-pyran-4-carboxamide (0.334 g, 0.886 mmol), NaHCO3 (0.149 g, 1.773 mmol) and 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.233 g, 1.064 mmol) in dioxane (4 mL) and water (1 mL) was sparged with Ar under sonication for 5 minutes, treated with Pd(PPh3)4 (0.102 g, 0.089 mmol), sparged again with Ar and heated at 95° C. overnight. The mixture was cooled to RT, diluted with THF and washed with brine. The aqueous layer was back-extracted with THF (3×) and the combined organics were dried over Na2SO4 and concentrated to dryness. The material was treated with MeCN and sonicated. The solids were collected via filtration and purified via silica gel chromatography (MeOH/EtOAc) to afford N-((5-((6′-methyl-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydro-2H-pyran-4-carboxamide (50 mg, 13%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.06 (s, 1H), 10.88 (s, 1H), 9.10 (d, J=2.3 Hz, 1H), 8.55 (d, J=5.7 Hz, 1H), 8.30-8.26 (m, 2H), 8.09 (d, J=9.0 Hz, 1H), 7.76 (dd, J=9.0, 2.9 Hz, 1H), 7.63 (d, J=2.4 Hz, 1H), 7.33 (d, J=8.2 Hz, 1H), 6.89 (dd, J=5.7, 2.4 Hz, 1H), 3.91-3.85 (m, 2H), 3.33-3.26 (m, 2H), 2.73-2.64 (m, 1H), 2.50 (s, 3H), 1.75-1.68 (m, 2H), 1.67-1.56 (m, 2H); MS (ESI) m/z: 432.1 (M−H+).

1. customwas sparged with Ar under sonication for 5 minutes
2. customsparged again with Ar
3. temperatureThe mixture was cooled to RT
4. additiondiluted with THF
5. washwashed with brine
6. extractionThe aqueous layer was back-extracted with THF (3×)
7. dry with materialthe combined organics were dried over Na2SO4
8. concentrationconcentrated to dryness
9. additionThe material was treated with MeCN
10. customsonicated
11. filtrationThe solids were collected via filtration
12. custompurified via silica gel chromatography (MeOH/EtOAc)