Reacción #595379

Ecuación de reacción

Tert-butyl 3-bromo-1H-indazole-1-carboxylate

1-(4-methoxybenzyl)-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-tetrazole

Sodium carbonate

→

3-(4-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)phenyl)-1H-indazole

Disolventes

1

1,1,1,3,3,3-hexafluoro-2-(4-(1-(2-(trifluoromethyl)phenylsulfonyl)-1H-indazol-3-yl)phenyl)propan-2-ol

1,4-dioxane

water

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe system was purged with nitrogen
2. 2
   Temperaturathe reaction mixture was heated overnight
3. 3
   Temperaturaat reflux temperature under a nitrogen atmosphere
4. 4
   Extracciónextracted with ethyl acetate
5. 5
   LavadoThe combined organic phases were washed with brine
6. 6
   Secadodried over magnesium sulfate
7. 7
   FiltraciónAfter filtration the solvent
8. 8
   Otrowas removed under reduced pressure
9. 9
   OtroThe residue was purified on SiO2 using 20 to 30% ethyl acetate in hexane as the eluent

Procedimiento

Tert-butyl 3-bromo-1H-indazole-1-carboxylate (5.0 g, 16.8 mmol) and a mixture of the regio-isomers of 1-(4-methoxybenzyl)-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-tetrazole (Example 19, step ii) (7.92 g, 20.2 mmol) were dissolved in 100 ml of a 1 to 1 mixture of 1,4-dioxane and water under a nitrogen atmosphere. Sodium carbonate (5.35 g, 50.5 mmol) was added and the system was purged with nitrogen. Then Pd(PPh3)4 (486 mg, 0.42 mmol) was added and the reaction mixture was heated overnight at reflux temperature under a nitrogen atmosphere. After cooling to room temperature the mixture was diluted with water and extracted with ethyl acetate. The combined organic phases were washed with brine, dried over magnesium sulfate. After filtration the solvent was removed under reduced pressure. The residue was purified on SiO2 using 20 to 30% ethyl acetate in hexane as the eluent to give 3-(4-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)phenyl)-1H-indazole as a mixture of two regioisomers in a 2 to 1 ratio (2.8 g) as a white solid.

Fuente