Lithium Hexamethyldisilazide → (2S)-2-[1-(2-chlorophenyl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-3-ethoxy-N-(5-methylpyrazin-2-yl)propanamide

HRID 1097992Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1097992
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:11]([O:13][CH2:14][C@H:15]([OH:26])[C:16]([NH:18][C:19]1[CH:24]=[N:23][C:22]([CH3:25])=[CH:21][N:20]=1)=[O:17])[CH3:12].Cl[C:28]1[N:33]=[CH:32][N:31]=[C:30]2[N:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[Cl:43])[N:35]=[CH:36][C:29]=12>C1COCC1.CCOC(C)=O>[Cl:43][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=1[N:34]1[C:30]2[N:31]=[CH:32][N:33]=[C:28]([O:26][C@@H:15]([CH2:14][O:13][CH2:11][CH3:12])[C:16]([NH:18][C:19]3[CH:24]=[N:23][C:22]([CH3:25])=[CH:21][N:20]=3)=[O:17])[C:29]=2[CH:36]=[N:35]1

Komponenten

6

Edukt 3

HCID 2733832Lithium HexamethyldisilazideHCID 112655704-Chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-D]pyrimidine2×HCID 57504485(S)-3-ethoxy-2-hydroxy-N-(5-methylpyrazin-2-yl)propanamide

Produkt 1

HCID 57504328(2S)-2-[1-(2-chlorophenyl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-3-ethoxy-N-(5-methylpyrazin-2-yl)propanamideAusbeute 72,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of lithium bis(trimethylsilyl)amide (1.398 mL, 1.40 mmol) was added dropwise to a stirred solution of (S)-3-ethoxy-2-hydroxy-N-(5-methylpyrazin-2-yl)propanamide (Intermediate H1) (315 mg, 1.40 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 and then a solution of 4-chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate B1) (371 mg, 1.40 mmol) in dry THF (3 mL) added dropwise over 1 minute and the reaction heated to 50° C. for 3 hours. The reaction mixture was diluted with EtOAc (50 mL), and washed sequentially with water (2×25 mL) and saturated brine (25 mL). The organic layer was dried (MgSO4) and evaporated. The residue was purified by flash silica chromatography with EtOAc to afford (2S)-2-[1-(2-chlorophenyl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-3-ethoxy-N-(5-methylpyrazin-2-yl)propanamide (460 mg, 72%).

Aufarbeitung

  1. temperaturethe reaction heated to 50° C. for 3 hours
  2. washwashed sequentially with water (2×25 mL) and saturated brine (25 mL)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. customevaporated
  5. customThe residue was purified by flash silica chromatography with EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-e0a1986446304c7eae8d526b14332686
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143263B2

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