Triethylamine → N-[(3R,6S)-1-(2-Methoxyethyl)-2-oxo-6-phenylazepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide

HRID 271944

Reaktionsgleichung

Reaktionsgleichung von HRID 271944
C(N(CC)CC)C.[NH2:8][C@@H:9]1[CH2:15][CH2:14][C@@H:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:12][N:11]([CH2:22][CH2:23][O:24][CH3:25])[C:10]1=[O:26].Cl[C:28](OC1C=CC([N+]([O-])=O)=CC=1)=[O:29].Cl.Cl.[O:42]=[C:43]1[NH:51][C:46]2=[N:47][CH:48]=[CH:49][CH:50]=[C:45]2[N:44]1[CH:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1.C(N(C(C)C)CC)(C)C.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.ClCCl>[CH3:25][O:24][CH2:23][CH2:22][N:11]1[CH2:12][C@H:13]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:14][CH2:15][C@@H:9]([NH:8][C:28]([N:55]2[CH2:56][CH2:57][CH:52]([N:44]3[C:45]4[C:46](=[N:47][CH:48]=[CH:49][CH:50]=4)[NH:51][C:43]3=[O:42])[CH2:53][CH2:54]2)=[O:29])[C:10]1=[O:26]

Komponenten

9

Edukt 6

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochlorideHCID 60037849(3R,6S)-3-Amino-1-(2-methoxyethyl)-6-phenylazepan-2-one

Produkt 1

HCID 11272121N-[(3R,6S)-1-(2-Methoxyethyl)-2-oxo-6-phenylazepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamideAusbeute 83 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Triethylamine (0.015 mL, 0.107 mmol) was added to a solution of (3R,6S)-3-amino-1-(2-methoxyethyl)-6-phenylazepan-2-one (28 mg, 0.107 mmol) and 4-nitrophenyl chloroformate (22 mg, 0.107 mmol) in tetrahydrofuran (2 mL) at 0° C. After 30 min, 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride (37 mg, 0.128 mmol), diisopropylethylamine (0.074 mL, 0.427 mmol) and dichloromethane (2.5 mL) were added and the mixture allowed to warm to ambient temperature. After 18 h, saturated aqueous sodium carbonate was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium carbonate (3×), saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→93% dichloromethane/methanol) gave the title compound (45 mg). MS 507.2737 (M+1).

Aufarbeitung

  1. waitAfter 18 h
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium carbonate (3×), saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (100% dichloromethane→93% dichloromethane/methanol)

Quellen und Nachweise

ORD-Eintrag
ord-237eaeac7073485ea79472d9917cbdb4
Quelldatensatz
uspto-grants-2008_11
Patentnummer
US07452903B2

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