1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-phenyl-1H-imidazole-4-carboxylic acid {2-[3-(2-chloro-phenoxy)-pyrrolidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093865Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1093865
CCN(C(C)C)C(C)C.[C:10]1([N:16]2[CH:20]=[C:19]([C:21]([NH:23][CH2:24][C:25]([OH:27])=O)=[O:22])[N:18]=[CH:17]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[Cl:50][C:51]1[CH:62]=[CH:61][CH:60]=[CH:59][C:52]=1[O:53][CH:54]1[CH2:58][CH2:57][NH:56][CH2:55]1>CN(C=O)C.O>[Cl:50][C:51]1[CH:62]=[CH:61][CH:60]=[CH:59][C:52]=1[O:53][CH:54]1[CH2:58][CH2:57][N:56]([C:25](=[O:27])[CH2:24][NH:23][C:21]([C:19]2[N:18]=[CH:17][N:16]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:20]=2)=[O:22])[CH2:55]1

Komponenten

8

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 450754773-(2-Chlorophenoxy)pyrrolidine hydrochlorideHCID 66591819[(1-phenyl-1H-imidazole-4-carbonyl)-amino]-acetic acid

Produkt 1

HCID 578744121-phenyl-1H-imidazole-4-carboxylic acid {2-[3-(2-chloro-phenoxy)-pyrrolidin-1-yl]-2-oxo-ethyl}-amideAusbeute 34,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

DIPEA (167.9 mg, 1.3 mmol) was added to a stirred solution of [(1-phenyl-1H-imidazole-4-carbonyl)-amino]-acetic acid (prepared from Intermediate 68 by means of Step 3 of the General Scheme) (80 mg, 0.32 mmol) in DMF (2 mL) followed by HOBt (48.3 mg, 0.35 mmol) and EDCI (124 mg, 0.65 mmol). After 2 minutes of stirring, 3-(2-chloro-phenoxy)-pyrrolidine hydrochloride (prepared by the method used for the synthesis of Intermediate 72) (76 mg, 0.32 mmol) was added and the resulting mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with cold water, extracted with ethyl acetate, dried over sodium sulfate, and concentrated under reduced pressure. Purification by recrystallisation from a mixture of DCM in hexane afforded 48 mg (34.7% Yield) of 1-phenyl-1H-imidazole-4-carboxylic acid {2-[3-(2-chloro-phenoxy)-pyrrolidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 425, 93.15%. 1H NMR (300 MHz, DMSO-d6): δ 8.4 (s, 1H), 8.3 (s, 1H), 8.1-8.0 (t, 1H), 7.8-7.7 (t, 2H), 7.5-7.4 (m, 2H), 7.4-7.2 (m, 2H), 7.06-7.0 (m, 1H), 5.3-5.1 (d, 1H), 4.2-4.0 (m, 2H), 4.0-3.5 (m, 4H), 2.3-2.2 (m, 1H), 2.2-2.0 (m, 1H).

Aufarbeitung

  1. additionwas added
  2. stirringthe resulting mixture was stirred at ambient temperature overnight
  3. extractionextracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification
  7. customby recrystallisation
  8. additionfrom a mixture of DCM in hexane

Quellen und Nachweise

ORD-Eintrag
ord-56e31f5beb8444a89ac026246f7b53cb
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08129376B2

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