Реакция #595379

Уравнение реакции

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

Растворители

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

Условия реакции

Обработка

1. 1
   Другоеthe system was purged with nitrogen
2. 2
   Температураthe reaction mixture was heated overnight
3. 3
   Температураat reflux temperature under a nitrogen atmosphere
4. 4
   Экстракцияextracted with ethyl acetate
5. 5
   ПромывкаThe combined organic phases were washed with brine
6. 6
   Сушкаdried over magnesium sulfate
7. 7
   ФильтрацияAfter filtration the solvent
8. 8
   Другоеwas removed under reduced pressure
9. 9
   ДругоеThe residue was purified on SiO2 using 20 to 30% ethyl acetate in hexane as the eluent

Методика

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.

Источник