Sodium cyanoborohydride → 5-Bromo-1-methyl-3-(4-(1-(oxetan-3-yl)piperidin-4-yl)phenylamino)-pyrazin-2(1H)-one

HRID 1919007Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1919007
[Br:1][C:2]1[N:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[O:23]1[CH2:26][C:25](=O)[CH2:24]1.C([BH3-])#N.[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[Br:1][C:2]1[N:3]=[C:4]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([CH:25]4[CH2:26][O:23][CH2:24]4)[CH2:19][CH2:18]3)=[CH:15][CH:16]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1

Komponenten

6

Edukt 3

HCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 580437455-Bromo-1-methyl-3-(4-(piperidin-4-yl)phenylamino)pyrazin-2(1H)-one

Produkt 1

HCID 670161765-Bromo-1-methyl-3-(4-(1-(oxetan-3-yl)piperidin-4-yl)phenylamino)-pyrazin-2(1H)-oneAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3007855ZincchlorideKatalysatorHCID 887MethanolLösungsmittel2×

Reaktionsbedingungen

Temperatur
48 °C

Versuchsvorschrift

A 100-mL sealed tube with a magnetic stirrer was purged with nitrogen and charged with 214a (390 mg, 1.08 mmol), oxetan-3-one (800 mg, 11 mmol) and methanol (10 mL). A suspension of sodium cyanoborohydride (208 mg, 3.3 mmol) and zinc chloride (225 mg, 1.65 mmol) in methanol (10 mL) was added, and the reaction was heated at 48° C. for 12 hours. After this time, the reaction mixture was concentrated, and the residue was partitioned between ethyl acetate (50 mL) and 10% aqueous potassium carbonate (10 mL). The aqueous layer was extracted with ethyl acetate (3×30 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica, 60:35:5 methylene chloride/diethyl ethyl/methanol) to afford a 60% yield (270 mg) of 5-bromo-1-methyl-3-(4-(1-(oxetan-3-yl)piperidin-4-yl)phenylamino)pyrazin-2(1H)-one (214b) as a yellow solid: MS (ESI+) m/z 421.2 (M+H).

Aufarbeitung

  1. customA 100-mL sealed tube with a magnetic stirrer
  2. customwas purged with nitrogen
  3. additionwas added
  4. concentrationAfter this time, the reaction mixture was concentrated
  5. customthe residue was partitioned between ethyl acetate (50 mL) and 10% aqueous potassium carbonate (10 mL)
  6. extractionThe aqueous layer was extracted with ethyl acetate (3×30 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by column chromatography (silica, 60:35:5 methylene chloride/diethyl ethyl/methanol)

Quellen und Nachweise

ORD-Eintrag
ord-930da94558cc4f839dadd9e439de2c20
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08618107B2

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