4-Methylmorpholine → (1RS,2S)-2-{(3RS)-4-Acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}methylcarbonylamino-3-phenyl-1-(1,3-thiazol-2-yl)-1-propanol

HRID 1061683Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1061683
CN1CCOCC1.[C:8]([N:11]1[CH:16]=[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:14]([CH2:23][C:24](O)=[O:25])[C:13](=[O:27])[CH:12]1[CH:28]([CH3:30])[CH3:29])(=[O:10])[CH3:9].ClC(OCC(C)C)=O.Cl.[NH2:40][C@@H:41]([CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[CH:42]([C:44]1[S:45][CH:46]=[CH:47][N:48]=1)[OH:43]>O1CCCC1.CS(C)=O.O>[C:8]([N:11]1[CH:16]=[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:14]([CH2:23][C:24]([NH:40][C@@H:41]([CH2:49][C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[CH:42]([C:44]2[S:45][CH:46]=[CH:47][N:48]=2)[OH:43])=[O:25])[C:13](=[O:27])[CH:12]1[CH:28]([CH3:30])[CH3:29])(=[O:10])[CH3:9]

Komponenten

8

Edukt 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 22284314{(3RS)-4-Acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}acetic acidHCID 69748243(1RS,2S)-2-amino-3-phenyl-1-(1,3-thiazol-2-yl)-1-propanol hydrochloride

Produkt 1

HCID 60073849(1RS,2S)-2-{(3RS)-4-Acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}methylcarbonylamino-3-phenyl-1-(1,3-thiazol-2-yl)-1-propanol

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-10 °C

Versuchsvorschrift

N-Methylmorpholine (66.4 μl) is added to a solution of {(3RS)-4-acetyl-3-isopropyl-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrazin-1-yl}acetic acid (162 mg, Reference compound No. 51-1) in tetrahydrofuran (2.5 ml). The mixture is cooled to −10° C., isobutyl chloroformate (65.4 μl) is added to the mixture, and the whole is stirred for 15 minutes. A mixed solution of (1RS,2S)-2-amino-3-phenyl-1-(1,3-thiazol-2-yl)-1-propanol hydrochloride (150 mg, Reference compound No. 10-2) and N-methylmorpholine (132.6 μl) in tetrahydrofuran (2.5 ml) and dimethyl sulfoxide (1 ml) is added thereto, and the whole is stirred overnight. Water is added to the reaction mixture, and the whole is extracted with ethyl acetate. The extract is washed with an aqueous sodium hydrogencarbonate solution, water and saturated brine successively and dried over magnesium sulfate. The extract is concentrated under reduced pressure, and the resulting residue is purified by column chromatography to give the titled compound (162.9 mg).

Aufarbeitung

  1. stirringthe whole is stirred overnight
  2. extractionthe whole is extracted with ethyl acetate
  3. washThe extract is washed with an aqueous sodium hydrogencarbonate solution, water and saturated brine successively
  4. dry with materialdried over magnesium sulfate
  5. concentrationThe extract is concentrated under reduced pressure
  6. customthe resulting residue is purified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-20062eec12b94237b3f5613ebb52f1fa
Quelldatensatz
uspto-grants-2005_11
Patentnummer
US06960575B2

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