1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 2405953Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2405953
[CH3:1][C:2]([S:19]([CH3:22])(=[O:21])=[O:20])([CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:10]=[CH:9]1)[C:3]([OH:5])=O.CCN=C=NCCCN(C)C.C1C=CC2[N:42]([OH:43])N=NC=2C=1.[O:44]1[CH2:49][CH2:48][CH2:47][CH2:46][CH:45]1NO>C(Cl)Cl.O>[CH3:1][C:2]([S:19]([CH3:22])(=[O:21])=[O:20])([CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:10]=[CH:9]1)[C:3]([NH:42][O:43][CH:45]1[CH2:46][CH2:47][CH2:48][CH2:49][O:44]1)=[O:5]

Komponenten

7

Edukt 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 13168123Tetrahydropyranyl hydroxylamineHCID 708175182-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)butanoic acid

Produkt 1

HCID 867102522-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideAusbeute 6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of 2-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)butanoic acid (304.6 mg, 0.945 mmol, 1 eq) in DCM (10 mL) was added TEA (172 mg, 1.70 mmol, 0.237 mL, 1.80 eq), EDCI (254 mg, 1.32 mmol, 1.4 eq), HOBT (260 mg 1.70 mmol, 1.80 eq) and O— tetrahydro-2-H-pyran-2-ylhydroxylamine (166 mg, 1.42 mmol, 1.5 eq). The reaction was allowed stir at RT overnight. The reaction mixture was diluted with DCM and water. The aqueous layer was extracted several times with DCM and the combined organic layers were dried (MgSO4), filtered and concentrated. The crude product mixture was absorbed onto silica gel and purified by flash chromatrography on silica gel eluting with an EtOAc-heptane gradient to give 2-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (24 mg, 6% yield). LC-MS M+H+422.6.

Aufarbeitung

  1. extractionThe aqueous layer was extracted several times with DCM
  2. dry with materialthe combined organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product mixture was absorbed onto silica gel
  6. custompurified by flash chromatrography on silica gel eluting with an EtOAc-heptane gradient

Quellen und Nachweise

ORD-Eintrag
ord-2235fbe2387e4b26a8fd0a1bbea7beec
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08809333B2

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