Diphosgene → (2S,3S)-2-{4-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide

HRID 32823

Reaktionsgleichung

Reaktionsgleichung von HRID 32823
[NH2:1][C@H:2]([C:27]1[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH2:35][N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)=[CH:29][CH:28]=1)[C:3]([NH:5][C@@H:6]([C@H:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:20])[C:7]([NH:9][C:10]1[S:11][CH:12]=[C:13]([C:15](=[O:18])[CH2:16][CH3:17])[N:14]=1)=[O:8])=[O:4].C(N(C(C)C)CC)(C)C.[O:51]=[C:52](Cl)OC(Cl)(Cl)Cl>O1CCCC1>[N:36]1([CH2:35][CH2:34][O:33][C:30]2[CH:31]=[CH:32][C:27]([CH:2]3[C:3](=[O:4])[N:5]([C@@H:6]([C@H:19]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH3:20])[C:7]([NH:9][C:10]4[S:11][CH:12]=[C:13]([C:15](=[O:18])[CH2:16][CH3:17])[N:14]=4)=[O:8])[C:52](=[O:51])[NH:1]3)=[CH:28][CH:29]=2)[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1

Komponenten

5

Edukt 3

HCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 86603387(2S,3S)-2-{(R)-2-amino-2-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-acetylamino}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide

Produkt 1

HCID 11642924(2S,3S)-2-{4-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

Crude (2S,3S)-2-{(R)-2-amino-2-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-acetylamino}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide (≈0.19 mmol) was dissolved in tetrahydrofuran (10 mL) that contained diisopropylethylamine (160 μL, 122 mg, 0.94 mmol) and was transferred via cannula to a solution of diphosgene (16 μL, 26 mg, 0.13 mmol) in tetrahydrofuran (15 mL) at 0° C. The reaction mixture was stirred for 20 minutes and then partitioned between ethyl acetate and water. The organic layer was separated and dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography over silica gel gradient eluted with 0-100% ethyl acetate in hexanes and the isolated material further purified by preparative thin layer chromatography using silica gel eluted with ethyl acetate. Precipitation of the isolated product from dichloromethane with an excess of hexanes gave (2S,3S)-2-{4-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide as an off white solid (32 mg, 29%).

Aufarbeitung

  1. custompartitioned between ethyl acetate and water
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by chromatography over silica gel gradient
  7. washeluted with 0-100% ethyl acetate in hexanes
  8. customthe isolated material further purified by preparative thin layer chromatography
  9. washeluted with ethyl acetate
  10. customPrecipitation of the isolated product from dichloromethane with an excess of hexanes

Quellen und Nachweise

ORD-Eintrag
ord-812e66f511de4271aab6d20fc643c8cf
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07427635B2

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