Hexane → (2S)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-ethoxy-N-(5-(methylthio)pyridin-2-yl)propanamide

HRID 1098145Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1098145
C[Al](C)C.CCCCCC.[CH3:11][S:12][C:13]1[CH:14]=[CH:15][C:16]([NH2:19])=[N:17][CH:18]=1.[Cl:20][C:21]1[C:22]([N:27]2[C:31]3=[N:32][CH:33]=[N:34][C:35]([O:36][C@@H:37]([CH2:42][O:43][CH2:44][CH3:45])[C:38](OC)=[O:39])=[C:30]3[CH:29]=[N:28]2)=[N:23][CH:24]=[CH:25][CH:26]=1>C1(C)C=CC=CC=1>[Cl:20][C:21]1[C:22]([N:27]2[C:31]3=[N:32][CH:33]=[N:34][C:35]([O:36][C@@H:37]([CH2:42][O:43][CH2:44][CH3:45])[C:38]([NH:19][C:16]4[CH:15]=[CH:14][C:13]([S:12][CH3:11])=[CH:18][N:17]=4)=[O:39])=[C:30]3[CH:29]=[N:28]2)=[N:23][CH:24]=[CH:25][CH:26]=1

Komponenten

6

Edukt 4

HCID 8058HexaneHCID 151797975-(Methylsulfanyl)pyridin-2-amineHCID 16682925TrimethylaluminumHCID 57504615methyl (2S)-2-[1-(3-chloropyridin-2-yl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-3-ethoxypropanoate

Produkt 1

HCID 57504501(2S)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-ethoxy-N-(5-(methylthio)pyridin-2-yl)propanamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

2M Trimethylaluminium in hexane (0.457 mL, 0.91 mmol) was added to 5-(methylthio)pyridin-2-amine (CAS no. 77618-99-6) (0.111 g, 0.79 mmol) in toluene (22 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. (2S)-methyl 2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-ethoxypropanoate (Intermediate L2) (0.300 g, 0.79 mmol) in toluene (6 mL) was added dropwise at this temperature. After the addition was complete, the solution was allowed to warm to ambient temperature and was then heated at reflux for 16 hours. The mixture was allowed to cool to ambient temperature and left standing for 2 days. The reaction mixture was concentrated, diluted with ethyl acetate (100 mL) then washed with saturated brine (50 mL). The organic layer was dried (MgSO4) and evaporated. The residue was purified by flash silica chromatography, eluting with 0 to 3% MeOH in DCM to afford the product.

Aufarbeitung

  1. customat 0° C.
  2. additionAfter the addition
  3. temperatureto warm to ambient temperature
  4. temperaturewas then heated
  5. temperatureat reflux for 16 hours
  6. temperatureto cool to ambient temperature
  7. waitleft
  8. waitstanding for 2 days
  9. concentrationThe reaction mixture was concentrated
  10. additiondiluted with ethyl acetate (100 mL)
  11. washthen washed with saturated brine (50 mL)
  12. dry with materialThe organic layer was dried (MgSO4)
  13. customevaporated
  14. customThe residue was purified by flash silica chromatography
  15. washeluting with 0 to 3% MeOH in DCM
  16. customto afford the product

Quellen und Nachweise

ORD-Eintrag
ord-893e4c1469ec46178be0b13a7c6cd6f8
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143263B2

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