Triethylamine → (2S,4S)-1-[[N-benzyloxycarbonyl-[4-(4-fluoropiperidin-1-yl)carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

HRID 227949

Reaktionsgleichung

Reaktionsgleichung von HRID 227949
Cl.[F:2][CH:3]1[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.C(N(CC)CC)C.[CH2:16]([O:23][C:24]([N:26]([CH2:47][C:48]([N:50]1[CH2:54][C@@H:53]([F:55])[CH2:52][C@H:51]1[C:56]#[N:57])=[O:49])[C:27]12[CH2:34][CH2:33][C:30]([C:35](ON3C4C=CC=CC=4N=N3)=[O:36])([CH2:31][CH2:32]1)[CH2:29][CH2:28]2)=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>O1CCCC1.ClCCl>[CH2:16]([O:23][C:24]([N:26]([CH2:47][C:48]([N:50]1[CH2:54][C@@H:53]([F:55])[CH2:52][C@H:51]1[C:56]#[N:57])=[O:49])[C:27]12[CH2:34][CH2:33][C:30]([C:35]([N:6]3[CH2:7][CH2:8][CH:3]([F:2])[CH2:4][CH2:5]3)=[O:36])([CH2:31][CH2:32]1)[CH2:29][CH2:28]2)=[O:25])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Komponenten

6

Edukt 3

HCID 8471TriethylamineHCID 27591584-Fluoropiperidine hydrochlorideHCID 57756828(2S,4S)-1-[(N-benzyloxycarbonyl-N-[4-(benzotriazol-1-yl)oxycarbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

Produkt 1

HCID 68843336(2S,4S)-1-[[N-benzyloxycarbonyl-[4-(4-fluoropiperidin-1-yl)carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrileAusbeute 78,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

4-Fluoropiperidine hydrochloride (18.2 mg) was suspended in tetrahydrofuran (0.87 mL). While this suspension was chilled in an ice bath, triethylamine (18.2 μL) was added and the mixture was stirred at the same temperature for 35 minutes. Subsequently, (2S,4S)-1-[[N-benzyloxycarbonyl-N-[4-(benzotriazol-1-yl)oxycarbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (50.0 mg) was added and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane and washed sequentially with 0.1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine. The organic layer was dried over anhydrous sodium sulfate and was concentrated under reduced pressure. The resulting residue was purified by column chromatography (eluant:ethyl acetate:methanol=20:1) to give (2S,4S)-1-[[N-benzyloxycarbonyl-[4-(4-fluoropiperidin-1-yl)carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (37.0 mg).

Aufarbeitung

  1. temperatureWhile this suspension was chilled in an ice bath
  2. stirringthe mixture was stirred at room temperature overnight
  3. washwashed sequentially with 0.1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationwas concentrated under reduced pressure
  6. customThe resulting residue was purified by column chromatography (eluant:ethyl acetate:methanol=20:1)

Quellen und Nachweise

ORD-Eintrag
ord-0b0f2c9c65124fed9eab8aa98b339649
Quelldatensatz
uspto-grants-2009_07
Patentnummer
US07560569B2

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