Triethylamine → 3-(4-(2-(2-(1H-Imidazol-4-yl)phenoxy)ethyl)phenyl)-1-hydroxy-1-(tetrahydro-2H-pyran-4-yl)urea

HRID 1023837Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1023837
C([N:20]1[CH:24]=[C:23]([C:25]2[CH:40]=[CH:39][CH:38]=[CH:37][C:26]=2[O:27][CH2:28][CH2:29][C:30]2[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][CH:31]=2)[N:22]=[CH:21]1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.Cl[C:42](Cl)([O:44]C(=O)OC(Cl)(Cl)Cl)Cl.C(N(CC)CC)C.[O:60]1[CH2:65][CH2:64][CH:63]([NH:66][OH:67])[CH2:62][CH2:61]1>ClCCl>[NH:20]1[CH:24]=[C:23]([C:25]2[CH:40]=[CH:39][CH:38]=[CH:37][C:26]=2[O:27][CH2:28][CH2:29][C:30]2[CH:31]=[CH:32][C:33]([NH:34][C:42](=[O:44])[N:66]([OH:67])[CH:63]3[CH2:64][CH2:65][O:60][CH2:61][CH2:62]3)=[CH:35][CH:36]=2)[N:22]=[CH:21]1

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 672072114-(2-(2-(1-Trityl-1H-imidazol-4-yl)phenoxy)ethyl)anilineHCID 82687656N-(tetrahydro-2H-pyran-4-yl)hydroxylamine

Produkt 1

HCID 1785220483-(4-(2-(2-(1H-Imidazol-4-yl)phenoxy)ethyl)phenyl)-1-hydroxy-1-(tetrahydro-2H-pyran-4-yl)ureaAusbeute 101,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 4-(2-(2-(1-trityl-1H-imidazol-4-yl)phenoxy)ethyl)aniline (113 mg, 0.217 mmol), triphosgene (21 mg, 0.07 mmol) and triethylamine (0.04 mL, 0.260 mmol) in dry dichloromethane (6 mL) was heated at reflux for 2 h and then cooled with an ice bath. To this mixture was added N-(tetrahydro-2H-pyran-4-yl)hydroxylamine (76 mg, 0.650 mmol). The reaction mixture was stirred at room temperature for 2 h. The solvent was removed and the crude was dissolved in methanol (4 mL) and acetic acid (1 mL). The reaction mixture was heated at 80° C. for 2 h. The reaction mixture was basified with aqueous 10% NaOH and the aqueous layer extracted with ethyl acetate (2×30 mL). The combined organic extracts were washed with brine (15 mL), dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography using 5% MeOH/dichloromethane as an eluent at afford the desired product as a yellowish solid (30 mg, 33%). 1H NMR: 1.63 (d, 2H, J=10.4 Hz), 1.98-2.07 (m, 2H), 3.15 (t, 3H, J=5.6 Hz), 3.46 (t, 2H, J=11.6 Hz), 3.78 (s, 1H), 4.02 (dd, 2H, J=11.2 Hz, 4 Hz), 4.36-4.45 (m, 4H), 6.98-7.03 (m, 3H), 7.19-7.27 (m, 3H), 7.30-7.42 (m, 3H), 7.66 (s, 1H), 8.14 (s, 1H).

Aufarbeitung

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. temperaturecooled with an ice bath
  4. customThe solvent was removed
  5. dissolutionthe crude was dissolved in methanol (4 mL)
  6. temperatureThe reaction mixture was heated at 80° C. for 2 h
  7. extractionthe aqueous layer extracted with ethyl acetate (2×30 mL)
  8. washThe combined organic extracts were washed with brine (15 mL)
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customThe residue was purified by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-d66f7b1f9b0a47a8b74d581eea2bb9d5
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08722720B2

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