Sodium hydride → HCID 57504622, Verbindung

HRID 1098140Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1098140
[H-].[Na+].[CH2:3]([O:5][CH2:6][C@H:7]([OH:12])[C:8]([O:10][CH3:11])=[O:9])[CH3:4].Cl[C:14]1[N:19]=[CH:18][N:17]=[C:16]2[N:20]([C:23]3[C:28]([C:29]([F:32])([F:31])[F:30])=[CH:27][C:26]([Cl:33])=[CH:25][N:24]=3)[N:21]=[CH:22][C:15]=12>O1CCCC1>[Cl:33][C:26]1[CH:27]=[C:28]([C:29]([F:32])([F:30])[F:31])[C:23]([N:20]2[C:16]3[N:17]=[CH:18][N:19]=[C:14]([O:12][C@@H:7]([CH2:6][O:5][CH2:3][CH3:4])[C:8]([O:10][CH3:11])=[O:9])[C:15]=3[CH:22]=[N:21]2)=[N:24][CH:25]=1

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 57438644methyl (2S)-3-ethoxy-2-hydroxypropanoateHCID 57504500HCID 57504500, Verbindung

Produkt 1

HCID 57504622HCID 57504622, VerbindungAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
5 °C

Versuchsvorschrift

60% Sodium hydride in mineral oil (0.316 g, 7.90 mmol) was added portionwise to (S)-methyl 3-ethoxy-2-hydroxypropanoate (Intermediate G4) (0.976 g, 6.59 mmol) in tetrahydrofuran (50 mL) cooled to 5° C. over a period of 1 minute under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes. A solution of 4-chloro-1-(5-chloro-3-(trifluoromethyl)pyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate K3) (1.1 g, 3.29 mmol) was added portionwise over a period of 1 minute. The resulting mixture was allowed to warm to ambient temperature and stirred for 2 hours. The mixture was cooled to 10° C., quenched with 1M citric acid (20 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with water (25 mL) and saturated brine (25 mL), dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 20 to 50% ethyl acetate in isohexane to give the product (1.1 g, 73%). 1H NMR (400 MHz, CDCl3) δ 1.25 (3H, t), 3.72 (2H, d), 3.81 (3H, s), 3.99-4.13 (2H, m), 5.84 (1H, dd), 8.22-8.24 (1H, m), 8.38 (1H, s), 8.57 (1H, s), 8.81-8.82 (1H, m); m/z (ESI+) (M+H)+=446; HPLC tR=2.52 min.

Aufarbeitung

  1. temperatureto warm to ambient temperature
  2. stirringstirred for 2 hours
  3. temperatureThe mixture was cooled to 10° C.
  4. customquenched with 1M citric acid (20 mL)
  5. extractionextracted with ethyl acetate (2×50 mL)
  6. washThe combined organic extracts were washed with water (25 mL) and saturated brine (25 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe crude product was purified by flash silica chromatography
  10. washeluting with 20 to 50% ethyl acetate in isohexane

Quellen und Nachweise

ORD-Eintrag
ord-c4142fb53cdc4beba8dd93febfb49fba
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143263B2

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