反应详情

温度

90 °C

A suspension of 2-chloro-4-((6-nitropyridin-3-yl)oxy)pyridine (14.38 g, 57.1 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (13.08 g, 62.9 mmol) and Cs2CO3 (55.9 g, 171 mmol) in DMF (150 mL) was sparged with Ar, treated with Pd(PPh3)4 (6.60 g, 5.71 mmol), sparged again with Ar and heated at 90° C. overnight. The mixture was cooled to RT, the solids removed via filtration through diatomaceous earth, washed with EtOAc and the filtrate concentrated to near-dryness. The residue was treated with EtOAc, washed with 5% LiCl (1×) and the aqueous layer back-extracted with EtOAc (4×). The combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford 2-(1-methyl-1H-pyrazol-4-yl)-4-((6-nitropyridin-3-yl)oxy)pyridine (12.28 g, 72%). 1H NMR (400 MHz, DMSO-d6): δ 8.59 (d, J=2.8 Hz, 1H), 8.49 (d, J=5.6 Hz, 1H), 8.41 (d, J=8.9 Hz, 1H), 8.29 (s, 1H), 8.00 (d, J=0.7 Hz, 1H), 7.97 (dd, J=8.9, 2.8 Hz, 1H), 7.44 (d, J=2.4 Hz, 1H), 6.97 (dd, J=5.6, 2.4 Hz, 1H), 3.85 (s, 3H); MS (ESI) m/z: 298.1 (M+H+).

1. customwas sparged with Ar
2. customsparged again with Ar
3. temperatureThe mixture was cooled to RT
4. customthe solids removed via filtration through diatomaceous earth
5. washwashed with EtOAc
6. concentrationthe filtrate concentrated to near-dryness
7. additionThe residue was treated with EtOAc
8. washwashed with 5% LiCl (1×)
9. extractionthe aqueous layer back-extracted with EtOAc (4×)
10. dry with materialThe combined organics were dried over Na2SO4
11. concentrationconcentrated to dryness
12. custompurified via silica gel chromatography (MeOH/DCM)