反应详情

温度

90 °C

A mixture of 5-((6-chloropyrimidin-4-yl)oxy)pyridin-2-amine (0.50 g, 2.246 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.467 g, 2.246 mmol), and Cs2CO3 (1.463 g, 4.49 mmol) in dioxane/H2O (5:1, 6 mL) was sparged with argon, treated with Pd(PPh3)4 (0.260 g, 0.225 mmol), sparged again with argon and heated at 90° C. overnight. The mixture was cooled to RT, the solids removed via filtration, rinsed with dioxane and the filtrate concentrated to dryness. The material was treated with EtOAc, the solid collected via filtration, rinsed with EtOAc and H2O and dried to obtain product. The layers of the filtrate were separated, the organic layer washed with brine, dried over Na2SO4, concentrated to dryness, triturated with EtOAc and the solid collected via filtration and combined with the above-isolated product to afford 5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-amine (410 mg, 68%). 1H NMR (400 MHz, DMSO-d6): δ 8.60 (d, J=1.1 Hz, 1H), 8.44 (s, 1H), 8.12 (s, 1H), 7.78 (d, J=2.9 Hz, 1H), 7.30-7.25 (m, 2H), 6.48 (d, J=8.9 Hz, 1H), 5.94 (s, 2H), 3.88 (s, 3H); MS (ESI) m/z: 269.1 (M+H+).

1. customwas sparged with argon
2. customsparged again with argon
3. temperatureThe mixture was cooled to RT
4. customthe solids removed via filtration
5. washrinsed with dioxane
6. concentrationthe filtrate concentrated to dryness
7. additionThe material was treated with EtOAc
8. filtrationthe solid collected via filtration
9. washrinsed with EtOAc and H2O
10. customdried
11. customto obtain product
12. customThe layers of the filtrate were separated
13. washthe organic layer washed with brine
14. dry with materialdried over Na2SO4
15. concentrationconcentrated to dryness
16. customtriturated with EtOAc
17. filtrationthe solid collected via filtration