Reacción #805363

Ecuación de reacción

1-(5-((2-Chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-3-(1-methylcyclopropyl)-1H-1,2,4-triazol-5(4H)-one

K2CO3

NH4Cl

1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

→

1-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-3-(1-methylcyclopropyl)-1H-1,2,4-triazol-5(4H)-one

Rendimiento 46.1%

Disolventes

dioxane

water

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe suspension was sonicated
2. 2
   Otrosparged with Ar for 10 min
3. 3
   Extracciónthe resultant emulsion was extracted with EtOAc (4×10 mL)
4. 4
   SecadoThe combined organics were dried (Na2SO4)
5. 5
   Concentraciónconcentrated in vacuo
6. 6
   OtroThe residue was purified by silica gel chromatography (MeOH/DCM)

Procedimiento

1-(5-((2-Chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-3-(1-methylcyclopropyl)-1H-1,2,4-triazol-5(4H)-one (0.10 g, 0.28 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.08 g, 0.36 mmol), and K2CO3 (0.10 g, 0.73 mmol) were suspended in dioxane (1.7 mL) and water (0.33 mL). The suspension was sonicated and sparged with Ar for 10 min. Pd(PPh3)4 (0.032 g, 0.028 mmol) was added and the reaction mixture was stirred at 85° C. for 12 h. Sat. NH4Cl (aq) (10 mL) was added and the resultant emulsion was extracted with EtOAc (4×10 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo. The residue was purified by silica gel chromatography (MeOH/DCM) to afford 1-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-3-(1-methylcyclopropyl)-1H-1,2,4-triazol-5(4H)-one (0.052 g, 46.1%) as an white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.76 (s, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.25 (s, 1H), 7.96 (s, 1H), 7.83 (d, J=8.8 Hz, 1H), 7.68 (d, J=8.8 Hz, 1H), 7.19 (d, J=2.4 Hz, 1H), 6.64 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 2.33 (s, 3H), 1.38 (s, 3H), 1.06 (d, J=2.3 Hz, 2H), 0.81 (t, J=2.3 Hz, 2H); MS (ESI) m/z: 404.2 (M+H+).

Fuente