Lithium Hexamethyldisilazide → HCID 57504307, Verbindung

HRID 1097985Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1097985
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[OH:11][CH:12]([CH:23]([CH3:25])[CH3:24])[C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][N:17]=1)=[O:14].Cl[C:27]1[N:32]=[CH:31][N:30]=[C:29]2[N:33]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=3[Cl:42])[N:34]=[CH:35][C:28]=12>C1COCC1.CCOC(C)=O>[Cl:42][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=1[N:33]1[C:29]2=[N:30][CH:31]=[N:32][C:27]([O:11][CH:12]([CH:23]([CH3:25])[CH3:24])[C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][N:17]=3)=[O:14])=[C:28]2[CH:35]=[N:34]1

Komponenten

6

Edukt 3

HCID 2733832Lithium HexamethyldisilazideHCID 112655704-Chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-D]pyrimidineHCID 574386132-hydroxy-3-methyl-N-(5-methylpyridin-2-yl)butanamide

Produkt 1

HCID 57504307HCID 57504307, VerbindungAusbeute 73,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel3×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of LHMDS (0.999 mL, 1.00 mmol) in anhydrous THF (15 mL) was added dropwise to a stirred solution of racemic 2-hydroxy-3-methyl-N-(5-methylpyridin-2-yl)butanamide C1 (208 mg, 1.00 mmol) in anhydrous THF (15 mL) over a period of 3 minutes under nitrogen. The resulting suspension was stirred at ambient temperature for 10 minutes, then a solution of 4-chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine B1 (265 mg, 1.00 mmol) in anhydrous THF (3 mL) was added dropwise over 1 minute and the resulting mixture heated to 50° C. for 3 hours. The mixture was allowed to cool to room temperature then diluted with EtOAc (50 mL), and washed sequentially with water (2×25 mL) and saturated brine (25 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The material was purified by flash silica chromatography, elution gradient 30 to 50% EtOAc in DCM. Pure fractions were evaporated to dryness to afford 2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-methyl-N-(5-methylpyridin-2-yl)butanamide (320 mg).

Aufarbeitung

  1. temperaturethe resulting mixture heated to 50° C. for 3 hours
  2. temperatureto cool to room temperature
  3. washwashed sequentially with water (2×25 mL) and saturated brine (25 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto afford crude product
  8. customThe material was purified by flash silica chromatography, elution gradient 30 to 50% EtOAc in DCM
  9. customPure fractions were evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-0a917ed5169e453a8348fd5b5bed07b8
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143263B2

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