Diisopropylethylamine → (3S)tetrahydro-3-furanyl N-[(1S,2R)-1-benzyl-4-(cyclopentyloxy)-2-hydroxy-4-(6-quinoxalinyl sulfonyl)butyl]carbamate

HRID 29188

Reaktionsgleichung

Reaktionsgleichung von HRID 29188
[NH2:1][C@@H:2]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C@H:3]([OH:25])[CH2:4][CH:5]([O:19][CH:20]1[CH2:24][CH2:23][CH2:22][CH2:21]1)[S:6]([C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][CH:13]=[N:12]2)(=[O:8])=[O:7].[C:33](=O)([O:42][C@H:43]1[CH2:47][CH2:46][O:45][CH2:44]1)[O:34]N1C(=O)CCC1=O.C(N(CC)C(C)C)(C)C>C(#N)C>[CH2:26]([C@H:2]([NH:1][C:33](=[O:34])[O:42][C@H:43]1[CH2:47][CH2:46][O:45][CH2:44]1)[C@H:3]([OH:25])[CH2:4][CH:5]([O:19][CH:20]1[CH2:21][CH2:22][CH2:23][CH2:24]1)[S:6]([C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][CH:13]=[N:12]2)(=[O:7])=[O:8])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 11229944Carbonic Acid 2,5-Dioxopyrrolidin-1-yl (S)-Tetrahydrofuran-3-yl EsterHCID 57187815(3R,4S)-4-amino-1-(cyclopentyloxy)-5-phenyl-1-(6-quinoxalinylsulfonyl)-3-pentanol

Produkt 1

HCID 21356359(3S)tetrahydro-3-furanyl N-[(1S,2R)-1-benzyl-4-(cyclopentyloxy)-2-hydroxy-4-(6-quinoxalinyl sulfonyl)butyl]carbamateAusbeute 86,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

A mixture of (3R,4S)-4-amino-1-(cyclopentyloxy)-5-phenyl-1-(6-quinoxalinylsulfonyl)-3-pentanol (50 mg, 0.110 mmoL), 2,5-dioxo-1-pyrrolidinyl [(3S)tetrahydro-3-furanyl] carbonate (28 mg, 0.121 mmol, WO 94/05639) and N,N-diisopropylethylamine (47.8 μL, 0.274 mmol) were combined under Argon at ambient temperature in approximately 1.5 mL of acetonitrile. After stirring for approximately 16 hours at ambient temperature, the reaction mixture was evaporated in vacuo and partitioned between ethyl acetate and aqueous potassium carbonate (5% w/v). The layers were separated and the aqueous layer was back extracted with ethyl acetate. The combined organic layers were washed twice with 1N sodium hydrogen sulfate. The acid layers were combined and back extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The residue was purified on a preparative TLC plate (20×20 cm, 1000 μM) eluting with 93:7 dichloromethane:methanol. The product band was removed, eluted with 3:1 methylene chloride:methanol, filtered, and evaporated in vacuo. The residue was crystallized with several drops of methanol. The residual solid was dried under high vacuum to provide (3S)tetrahydro-3-furanyl N-[(1S,2R)-1-benzyl-4-(cyclopentyloxy)-2-hydroxy-4-(6-quinoxalinyl sulfonyl)butyl]carbamate (54 mg, 86%) as a white solid. H1-NMR (chloroform-D3): 1.61 (m, 5H), 1.86 (m, 4H), 2.09 (m, 1H), 2.97 (m, 3H), 3.20 (m, 2H), 3.80 (m, 6H), 4.83 (m, 1H), 4.93 (m, 1H), 5.14 (m, 1H), 7.28 (m, 5H), 8.13 (m, 1H), 8.31 (d, 1H), 8.69 (d, 1H), 9.05 (s, 2H). MS(ESI): 571(M+H).

Aufarbeitung

  1. customthe reaction mixture was evaporated in vacuo
  2. custompartitioned between ethyl acetate and aqueous potassium carbonate (5% w/v)
  3. customThe layers were separated
  4. extractionthe aqueous layer was back extracted with ethyl acetate
  5. washThe combined organic layers were washed twice with 1N sodium hydrogen sulfate
  6. extractionback extracted with ethyl acetate
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe residue was purified on a preparative TLC plate (20×20 cm, 1000 μM)
  12. washeluting with 93:7 dichloromethane
  13. customThe product band was removed
  14. washeluted with 3:1 methylene chloride
  15. filtrationmethanol, filtered
  16. customevaporated in vacuo
  17. customThe residue was crystallized with several drops of methanol
  18. customThe residual solid was dried under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-3b992ddf3fde498dbeb8d0f871a84a40
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07419967B2

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