Triethylamine → N-[5-(2,3-Difluorophenyl)-1-(2-methoxyethyl)-2-oxopiperidin-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide

HRID 20176

Reaktionsgleichung

Reaktionsgleichung von HRID 20176
C(N(CC)CC)C.[NH2:8][CH:9]1[CH2:14][CH:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=2[F:22])[CH2:12][N:11]([CH2:23][CH2:24][O:25][CH3:26])[C:10]1=[O:27].C1C([N+]([O-])=O)=CC=C([Cl-][C:38]([O-])=[O:39])C=1.Cl.Cl.[O:43]=[C:44]1[NH:52][C:47]2=[N:48][CH:49]=[CH:50][CH:51]=[C:46]2[N:45]1[CH:53]1[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1.C(=O)(O)[O-].[Na+]>O1CCCC1>[F:22][C:16]1[C:17]([F:21])=[CH:18][CH:19]=[CH:20][C:15]=1[CH:13]1[CH2:12][N:11]([CH2:23][CH2:24][O:25][CH3:26])[C:10](=[O:27])[CH:9]([NH:8][C:38]([N:56]2[CH2:57][CH2:58][CH:53]([N:45]3[C:46]4[C:47](=[N:48][CH:49]=[CH:50][CH:51]=4)[NH:52][C:44]3=[O:43])[CH2:54][CH2:55]2)=[O:39])[CH2:14]1

Komponenten

6

Edukt 4

HCID 8471Triethylamine2×HCID 516892Sodium BicarbonateHCID 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochlorideHCID 222931943-Amino-5-(2,3-difluorophenyl)-1-(2-methoxyethyl)piperidin-2-one

Produkt 1

HCID 22293309N-[5-(2,3-Difluorophenyl)-1-(2-methoxyethyl)-2-oxopiperidin-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamideAusbeute 42,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Triethylamine (83 μL, 0.598 mmol) was added to a solution of 3-amino-5-(2,3-difluorophenyl)-1-(2-methoxyethyl)piperidin-2-one (170 mg, 0.598 mmol) and 4-nitrophenylchloroformate (121 mg, 0.598 mmol) in tetrahydrofuran (4 mL) at 0° C. After 1 h, 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride (174 mg, 0.651 mmol), triethylamine (249 μL, 1.794 mmol) were added and the mixture allowed to warm to ambient temperature. After 18 h, saturated aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate (3×), saturated brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography [100% dichloromethane→95% dichloromethane/5% (10% ammonium hydroxide/methanol)] gave the title compound (0.135 g). MS 529.2353 (M+1). 1H NMR (500 MHz, CDCl3) δ 8.03 (dd, J=5.3, 1.1 Hz, 1H), 7.38 (dd, J=7.8, 1.2 Hz, 1H), 7.11-7.03 (m, 2H), 7.01-6.96 (m, 2H), 5.82 (d, J=3.4 Hz, 1H), 4.58-4.53 (m, 1H), 4.34-4.30 (m, 1H), 4.23 (d, J=6.6 Hz, 2H), 3.71-3.62 (m, 3H), 3.60-3.53 (m, 3H), 3.52-3.46 (m, 1H), 3.33 (s, 3H), 2.96 (dd, J=23.4, 10.5 Hz, 2H), 2.80-2.78 (m, 1H), 2.28-2.21 (m, 2H), 1.90 (dd, J=10.5, 2.0 Hz, 2H).

Aufarbeitung

  1. waitAfter 18 h
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium bicarbonate (3×), saturated brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography [100% dichloromethane→95% dichloromethane/5% (10% ammonium hydroxide/methanol)]

Quellen und Nachweise

ORD-Eintrag
ord-a469572c059645ad85899dea393245e3
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745427B2

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