Sodium hydride → tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

HRID 387523

Reaktionsgleichung

Reaktionsgleichung von HRID 387523
[Br:1][C:2]1[CH:7]=[N:6][C:5]2[N:8]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[N:9]=[CH:10][C:4]=2[C:3]=1O.[H-].[Na+].FC(F)(F)S(N(C1C=CC=CC=1)S(C(F)(F)F)(=O)=O)(=O)=O.[N:44]1([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1.[NH4+].[Cl-]>CN(C=O)C.CCOC(C)=O.O>[Br:1][C:2]1[C:3]([N:47]2[CH2:46][CH2:45][N:44]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:49][CH2:48]2)=[C:4]2[CH:10]=[N:9][N:8]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[C:5]2=[N:6][CH:7]=1

Komponenten

9

Edukt 5

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 142176Phenyl triflimideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 178490902HCID 178490902, Verbindung

Produkt 1

HCID 68760849tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylateAusbeute 91 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

A solution of 5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (10.85 g, 32.5 mmol) in DMF (130 mL) was added dropwise to a stirred suspension of sodium hydride (60% in mineral oil, 1.56 g, 39 mmol) in DMF (70 mL) at room temperature. Once the addition was complete, the mixture was stirred at 40° C. for 30 minutes. The resulting solution was cooled to room temperature and treated with 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (13.92 g, 38.96 mmol). After 1 hour, solid tert-butyl piperazine-1-carboxylate (13.3 g, 71.43 mmol) was added in 2 portions with stirring, and the mixture was stirred at 80° C. for 1.5 hours. The resulting mixture was allowed to cool to room temperature overnight. Saturated NH4Cl solution (100 mL), water (50 mL) and EtOAc (250 mL) were then added to the reaction mixture. The phases were separated, and the aqueous layer was extracted with EtOAc (2×50 mL). The combined organic phases were washed with water (1×50 mL), dried (MgSO4), filtered, and concentrated in vacuo. The residue obtained was crystallized from boiling EtOAc (˜30 mL) and hexane (˜10 mL). The solid formed was filtered, washed with additional hexane (2×10 mL), and dried to provide tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (14.8 g, 91% yield) as a solid. LCMS (APCI+) m/z 504 (M+H)+, Retention time=4.56 minutes.

Aufarbeitung

  1. additionOnce the addition
  2. temperatureThe resulting solution was cooled to room temperature
  3. waitAfter 1 hour
  4. stirringwith stirring
  5. stirringthe mixture was stirred at 80° C. for 1.5 hours
  6. temperatureto cool to room temperature overnight
  7. customThe phases were separated
  8. extractionthe aqueous layer was extracted with EtOAc (2×50 mL)
  9. washThe combined organic phases were washed with water (1×50 mL)
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue obtained
  14. customwas crystallized
  15. customThe solid formed
  16. filtrationwas filtered
  17. washwashed with additional hexane (2×10 mL)
  18. customdried

Quellen und Nachweise

ORD-Eintrag
ord-3173526cff904050ad0f8d3e8180ba80
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08372842B2

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