反应详情

温度

95 °C

A mixture of Example C1 (0.250 g, 0.598 mmol), K2CO3 (0.165 g, 1.197 mmol) and 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.157 g, 0.718 mmol) in dioxane (8 mL) and water (2 mL) was sparged with Ar, treated with Pd(PPh3)4 (0.069 g, 0.060 mmol), sparged again with Ar and heated at 95° C. for 36 h. The mixture was cooled to RT, treated with satd. NaHCO3 and extracted with EtOAc (4×). The combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-(5-((2′-methyl-[2,4′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (56 mg, 20%). 1H NMR (400 MHz, DMSO-d6): δ 10.98 (s, 1 H), 8.59 (d, J=5.6 Hz, 1 H), 8.52 (d, J=5.2 Hz, 1H), 8.27 (d, J=3.0 Hz, 1 H), 8.08 (d, J=9.1 Hz, 1 H), 7.89 (s, 1 H), 7.81-7.74 (m, 2 H), 7.70 (d, J=2.4 Hz, 1 H), 6.97 (dd, J=5.6, 2.4 Hz, 1 H), 3.93-3.78 (m, 5 H), 3.49-3.35 (m, 4 H), 2.52 (s, 3 H), 1.77-1.65 (m, 2 H), 1.62-1.56 (m, 2H); MS (ESI) m/z: 475.2 (M+H+).

1. customsparged again with Ar
2. temperatureThe mixture was cooled to RT
3. additiontreated with satd
4. extractionNaHCO3 and extracted with EtOAc (4×)
5. dry with materialThe combined organics were dried over Na2SO4
6. concentrationconcentrated to dryness
7. custompurified via silica gel chromatography (MeOH/DCM)