Triethylamine → N-[(3R,6S)-6-(2,3-difluorophenyl)-7-(hydroxymethyl)-2-oxoazepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide

HRID 967599Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 967599
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]=[C:18]([F:22])[C:17]=2[F:23])[CH:12]([CH2:24][OH:25])[NH:11][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>O1CCCC1.C(Cl)(Cl)Cl>[F:23][C:17]1[C:18]([F:22])=[CH:19][CH:20]=[CH:21][C:16]=1[C@H:13]1[CH:12]([CH2:24][OH:25])[NH:11][C:10](=[O:26])[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])[CH2:15][CH2:14]1

Komponenten

7

Edukt 4

HCID 8471Triethylamine2×HCID 821294-Nitrophenyl chloroformateHCID 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochlorideHCID 66939139HCID 66939139, Verbindung

Produkt 1

HCID 60037851N-[(3R,6S)-6-(2,3-difluorophenyl)-7-(hydroxymethyl)-2-oxoazepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamideAusbeute 15,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6212ChloroformLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Triethylamine (0.68 mL, 0.49 mmol) was added to a solution of (3R,6S)-3-amino-6-(2,3-difluorophenyl)-7-(hydroxymethyl)azepan-2-one (57 mg, 0.21 mmol) and 4-nitrophenyl chloroformate (47 mg, 0.23 mmol) in tetrahydrofuran (10 mL) at 0° C. After 30 min, 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride (98 mg, 0.34 mmol), triethylamine (0.84 mmol) and chloroform (10 mL) were added and the mixture allowed to warm to ambient temperature. The reaction was stirred overnight, concentrated, diluted with saturated aqueous sodium bicarbonate and extracted with dichloromethane (2×). The organic layer was washed with water, saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (1%→12% methanol/dichloromethane) gave the title compound (17 mg). MS 515.2203 (M+1).

Aufarbeitung

  1. concentrationconcentrated
  2. additiondiluted with saturated aqueous sodium bicarbonate
  3. extractionextracted with dichloromethane (2×)
  4. washThe organic layer was washed with water, saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (1%→12% methanol/dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-2e2bac05e49d4830a3d69c4160bb2c0c
Quelldatensatz
uspto-grants-2005_10
Patentnummer
US06953790B2

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