Water → Bisegliptin

HRID 555679

Reaktionsgleichung

Reaktionsgleichung von HRID 555679
[NH2:1][C:2]12[CH2:9][CH2:8][C:5]([C:10]([O:12][CH2:13][CH3:14])=[O:11])([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.C(NC(C)C)(C)C.Br[CH2:23][C:24]([N:26]1[CH2:30][C@@H:29]([F:31])[CH2:28][C@H:27]1[C:32]#[N:33])=[O:25].O>C(#N)C>[CH2:13]([O:12][C:10]([C:5]12[CH2:4][CH2:3][C:2]([NH:1][CH2:23][C:24]([N:26]3[CH2:30][C@@H:29]([F:31])[CH2:28][C@H:27]3[C:32]#[N:33])=[O:25])([CH2:9][CH2:8]1)[CH2:7][CH2:6]2)=[O:11])[CH3:14]

Komponenten

6

Edukt 4

HCID 962WaterHCID 7912DiisopropylamineHCID 21090395(2S,4S)-1-(2-bromoacetyl)-4-fluoropyrrolidine-2-carbonitrileHCID 23149693Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate

Produkt 1

HCID 11688894BisegliptinAusbeute 88,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel2×

Versuchsvorschrift

Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (92.0 mg) was dissolved in acetonitrile (2 mL) and diisopropylamine (100 μL) was added to the solution. While the mixture was chilled in an ice bath, (2S,4S)-1-(2-bromoacetyl)-4-fluoropyrrolidine-2-carbonitrile (100 mg) in acetonitrile (1 mL) was added dropwise. The mixture was stirred for 1.5 hours while chilled in the ice bath. Subsequently, water was added and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluant:ethyl acetate:methanol=5:1) to give (2S,4S)-1-[[N-(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (132 mg).

Aufarbeitung

  1. temperatureWhile the mixture was chilled in an ice bath
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (eluant:ethyl acetate:methanol=5:1)

Quellen und Nachweise

ORD-Eintrag
ord-abd12d98ef3847688f3fd8778320c291
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08053465B2

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