Diphosgene → (2S,3S)-N-(4-acetyl-thiazol-2-yl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-butyramide

HRID 32809

Reaktionsgleichung

Reaktionsgleichung von HRID 32809
[C:1]([C:4]1[N:5]=[C:6]([NH:9][C:10](=[O:33])[C@@H:11]([NH:20][C:21](=[O:32])[C@H:22]([NH2:31])[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH3:13])[S:7][CH:8]=1)(=[O:3])[CH3:2].C(N(C(C)C)CC)(C)C.[O:43]=[C:44](Cl)OC(Cl)(Cl)Cl>O1CCCC1.C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:1]([C:4]1[N:5]=[C:6]([NH:9][C:10](=[O:33])[C@@H:11]([N:20]2[C:21](=[O:32])[C@@H:22]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[NH:31][C:44]2=[O:43])[C@H:12]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH3:13])[S:7][CH:8]=1)(=[O:3])[CH3:2]

Komponenten

7

Edukt 3

HCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 86603380(2S,3S)-N-(4-acetyl-thiazol-2-yl)-2-[(R)-2-amino-2-(4-methoxy-phenyl)-acetylamino]-3-phenyl-butyramide

Produkt 1

HCID 11648879(2S,3S)-N-(4-acetyl-thiazol-2-yl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-butyramideAusbeute 119,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 1140TolueneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

(2S,3S)-N-(4-Acetyl-thiazol-2-yl)-2-[(R)-2-amino-2-(4-methoxy-phenyl)-acetylamino]-3-phenyl-butyramide (2.7 g, 90% purity, 5.2 mmol) and diisopropylethylamine (4.2 mL, 23.6 mmol) in tetrahydrofuran (50 mL) were added to a solution of diphosgene (0.48 mL, 4 mmol) in a mixture of toluene (50 mL) and tetrahydrofuran (50 mL) over 10 minutes at 0° C. The mixture was stirred at 0° C. for 20 minutes and diluted with ethyl acetate. The mixture was washed with water, brine and dried (sodium sulfate). Evaporation of the solvents and chromatography of the residue over silica gel with 0.4-1% v/v methanol in dichloromethane gave (2S,3S)-N-(4-acetyl-thiazol-2-yl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-butyramide (2.36 g, 92%) as a white solid.

Aufarbeitung

  1. washThe mixture was washed with water, brine
  2. dry with materialdried (sodium sulfate)
  3. customEvaporation of the solvents and chromatography of the residue over silica gel with 0.4-1% v/v methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-269506ebc9e54b1dac5e31a8e9d82d6e
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07427635B2

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