Water → N-[(3R,6S)-6-(2,3-Difluorophenyl)-2-thioxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide

HRID 14397

Reaktionsgleichung

Reaktionsgleichung von HRID 14397
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])[CH2:12][N:11]([CH2:24][C:25]([F:28])([F:27])[F:26])[C:10]1=[S:29].[O:30]=[C:31]1[NH:39][C:34]2=[N:35][CH:36]=[CH:37][CH:38]=[C:33]2[N:32]1[CH:40]1[CH2:45][CH2:44][N:43]([C:46](Cl)=[O:47])[CH2:42][CH2:41]1.O>ClCCl>[F:23][C:17]1[C:18]([F:22])=[CH:19][CH:20]=[CH:21][C:16]=1[C@H:13]1[CH2:12][N:11]([CH2:24][C:25]([F:27])([F:28])[F:26])[C:10](=[S:29])[C@H:9]([NH:8][C:46]([N:43]2[CH2:42][CH2:41][CH:40]([N:32]3[C:33]4[C:34](=[N:35][CH:36]=[CH:37][CH:38]=4)[NH:39][C:31]3=[O:30])[CH2:45][CH2:44]2)=[O:47])[CH2:15][CH2:14]1

Komponenten

6

Edukt 4

HCID 962WaterHCID 8471TriethylamineHCID 222932214-(2-Oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carbonyl chlorideHCID 86616757(3R,6S)-3-Amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepane-2-thione

Produkt 1

HCID 86616758N-[(3R,6S)-6-(2,3-Difluorophenyl)-2-thioxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamideAusbeute 55,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Triethylamine (100 μL, 0.720 mmol) was added to a solution of the bis hydrochloride salt of (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepane-2-thione (90 mg, 0.240 mmol) and 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carbonyl chloride (74 mg, 0.264 mmol) in dichloromethane (10 mL) and the mixture heated to reflux. After 18 h, the reaction was allowed to cool to ambient temperature, water was added and the mixture was extracted with dichloromethane (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. Purification by silica gel chromatography (100% dichloromethane→95% dichloromethane/methanol) gave the title compound (78 mg). MS 583.2 (M+1).

Aufarbeitung

  1. temperaturethe mixture heated to reflux
  2. extractionthe mixture was extracted with dichloromethane (3×)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (100% dichloromethane→95% dichloromethane/methanol)

Quellen und Nachweise

ORD-Eintrag
ord-aa1b893dcf154e85b3ad2cfec0553e85
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07732438B2

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