Potassium Carbonate → 3-((3-Cyclopropyl-4-nitro-1H-indazol-1-yl)methyl)-1-methylpyridin-2(1H)-one

HRID 79428

Reaktionsgleichung

Reaktionsgleichung von HRID 79428
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[N+:11]([O-:13])=[O:12])[N:4]([CH2:14][C:15]2[C:16](=[O:22])[N:17]([CH3:21])[CH:18]=[CH:19][CH:20]=2)[N:3]=1.[CH:23]1(B(O)O)[CH2:25][CH2:24]1.C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=C(S([O-])(=O)=O)C=2OC)CCCCC1.[Na+].C1OCCOC1.O>[CH:23]1([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][C:9]=3[N+:11]([O-:13])=[O:12])[N:4]([CH2:14][C:15]3[C:16](=[O:22])[N:17]([CH3:21])[CH:18]=[CH:19][CH:20]=3)[N:3]=2)[CH2:25][CH2:24]1

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 672613133-((3-bromo-4-nitro-1H-indazol-1-yl)methyl)-1-methylpyridin-2(1H)-one

Produkt 1

HCID 672604333-((3-Cyclopropyl-4-nitro-1H-indazol-1-yl)methyl)-1-methylpyridin-2(1H)-oneAusbeute 83,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 23677046Sodium 2'-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl-3-sulfonateKatalysatorHCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Versuchsvorschrift

To a 50 mL pear shaped flask was added 4-dioxane/water (3.2 mL/0.6 mL). The flask was cooled in an ice/water bath before applying vacuum for 20 minutes. 3-((3-Bromo-4-nitro-1H-indazol-1-yl)methyl)-1-methylpyridin-2(1H)-one (0.55 g, 1.52 mmol), cyclopropylboronic acid (0.33 g, 3.79 mmol), sodium 2′-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl-3-sulfonate (0.047 g, 0.091 mmol), palladium acetate (0.01 g, 0.4 mmol), and potassium carbonate (0.84 g, 6.07 mmol) were combined in a 25 mL round bottom flask and placed under vacuum. The degassed solvent mixture was added to the solid reagents and the flask was affixed with a condenser. The apparatus was evacuated and back filled with argon 5 times before heating at reflux under argon for 5 hours. The mixture was cooled to ambient temperature and filtered through a pad of Celite®. The filter cake was washed with ethyl acetate and water. The filtrate phases were separated and the aqueous phase was extracted with ethyl acetate 3 times. The combined organic extracts were washed with saturated sodium bicarbonate 3 times. The organic phase was concentrated under vacuum and dried under high vacuum to give 3-((-cyclopropyl-4-nitro-1H-indazol-1-yl)methyl)-1-methylpyridine-2(1H)-one as a beige solid (413 mg).

Aufarbeitung

  1. temperatureThe flask was cooled in an ice/water bath
  2. customfor 20 minutes
  3. additionThe degassed solvent mixture was added to the solid reagents
  4. customthe flask was affixed with a condenser
  5. customThe apparatus was evacuated
  6. additionback filled with argon 5 times
  7. temperaturebefore heating
  8. temperatureat reflux under argon for 5 hours
  9. filtrationfiltered through a pad of Celite®
  10. washThe filter cake was washed with ethyl acetate and water
  11. customThe filtrate phases were separated
  12. extractionthe aqueous phase was extracted with ethyl acetate 3 times
  13. washThe combined organic extracts were washed with saturated sodium bicarbonate 3 times
  14. concentrationThe organic phase was concentrated under vacuum
  15. customdried under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-3e16bca523634c25bb9d39cba49681b2
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841455B2

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