Citric Acid → (S)-2-(1-benzyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-methylpyridin-2-yl)propanamide

HRID 1098207Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1098207
[H-].[Na+].[Si:3]([O:20][CH2:21][CH2:22][O:23][CH2:24][C@H:25]([OH:36])[C:26]([NH:28][C:29]1[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][N:30]=1)=[O:27])([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH2:37]([N:44]1[C:48]2=[N:49][CH:50]=[N:51][C:52](Cl)=[C:47]2[CH:46]=[N:45]1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.O.CCOC(C)=O>[CH2:37]([N:44]1[C:48]2=[N:49][CH:50]=[N:51][C:52]([O:36][C@@H:25]([CH2:24][O:23][CH2:22][CH2:21][O:20][Si:3]([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=3)[C:26]([NH:28][C:29]3[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][N:30]=3)=[O:27])=[C:47]2[CH:46]=[N:45]1)[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Komponenten

8

Edukt 4

HCID 311Citric AcidHCID 24758Sodium hydrideHCID 114250891-benzyl-4-chloro-1H-pyrazolo[3,4-d]pyrimidineHCID 57504665(S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxy-N-(5-methylpyridin-2-yl)propanamide

Produkt 1

HCID 57504536(S)-2-(1-benzyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-methylpyridin-2-yl)propanamideAusbeute 77,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Sodium hydride (90 mg, 2.25 mmol) was added to (S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxy-N-(5-methylpyridin-2-yl)propanamide (538 mg, 1.12 mmol) (Intermediate AU2) in anhydrous THF (20 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then 1-benzyl-4-chloro-1H-pyrazolo[3,4-d]pyrimidine (Intermediate AL2) (250 mg, 1.02 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was neutralised with 1M citric acid, diluted with water (20 mL) and EtOAc (50 mL). The organic layer was separated and the aqueous layer re-extracted with EtOAc (2×50 mL). The combined organics were washed with saturated brine (75 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash silica chromatography, elution gradient 30 to 50% EtOAc in isohexane to afford the product (540 mg, 77%). m/z (ES+) (M+H)+=687; HPLC tR=3.89 min.

Aufarbeitung

  1. temperatureto warm to room temperature
  2. stirringstirred overnight
  3. customThe organic layer was separated
  4. extractionthe aqueous layer re-extracted with EtOAc (2×50 mL)
  5. washThe combined organics were washed with saturated brine (75 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash silica chromatography, elution gradient 30 to 50% EtOAc in isohexane

Quellen und Nachweise

ORD-Eintrag
ord-c3a4ace8b6954a54b40f3d6700eb53e8
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143263B2

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