Reaktion #166665

Reaktionsgleichung

1-((5-(benzyloxy)-6-methylpyridin-2-yl)methyl)-3-bromo-4-nitro-1H-indazole

cyclopropylboronic acid

K2CO3

sodium 2′-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl-3-sulfonate

→

desired product

1-((5-(benzyloxy)-6-methylpyridin-2-yl)methyl)-3-cyclopropyl-4-nitro-1H-indazole

Lösungsmittel

1,4-dioxane H2O

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe second flask was also evacuated with vacuum
2. 2
   workup.ADDITIONback filled with N2 for 3 times
3. 3
   SonstigeThe cold degassed dioxane/H2O
4. 4
   workup.ADDITIONwas added to the second flask, which
5. 5
   Sonstigewas evacuated with vacuum
6. 6
   workup.ADDITIONback filled with argon for 5 times
7. 7
   workup.ADDITIONThe reaction mix
8. 8
   Temperaturwas then heated to 80° C. for 3 hours
9. 9
   Sonstigereaction at this point
10. 10
    TemperaturThe reaction was cooled to ambient temperature
11. 11
    Filtrationfiltered
12. 12
    Einengenconcentrated under reduced pressure
13. 13
    workup.ADDITIONThe residue was diluted with EtOAc (200 mL)
14. 14
    WaschenThe organic layer was washed with saturated NaHCO3
15. 15
    Trocknendried (Na2SO4)
16. 16
    Einengenconcentrated

Vorschrift

A first flask was charged with 1,4-dioxane/H2O (50 mL/10 mL). The flask was cooled to 0° C. and vacuum was applied for 20 minutes. A second flask was charged with 1-((5-(benzyloxy)-6-methylpyridin-2-yl)methyl)-3-bromo-4-nitro-1H-indazole (6.07 g, 13.4 mmol), cyclopropylboronic acid (4.60 g, 53.6 mmol), diacetoxypalladium (0.150 g, 0.670 mmol), K2CO3 (5.55 g, 40.2 mmol) and sodium 2′-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl-3-sulfonate (0.686 g, 1.34 mmol). The second flask was also evacuated with vacuum and back filled with N2 for 3 times. The cold degassed dioxane/H2O was added to the second flask, which was evacuated with vacuum and back filled with argon for 5 times. The reaction mix was then heated to 80° C. for 3 hours. A sample (1H NMR) taken from the flask showed complete reaction at this point. The reaction was cooled to ambient temperature, filtered and concentrated under reduced pressure. The residue was diluted with EtOAc (200 mL). The organic layer was washed with saturated NaHCO3, dried (Na2SO4) and concentrated to give desired product, which was used in the next step without further purification.

Quelle