Triethylamine → HCID 44200596, Verbindung

HRID 2400378Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2400378
[Cl:1][C:2]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]2[CH2:11][N:12]3[C:19]([C:20]4([C:23]([F:26])([F:25])[F:24])[CH2:22][CH2:21]4)=[CH:18][N:17]=[C:13]3[C@H:14]([NH2:16])[CH2:15][C:4]=2[CH:3]=1.C(N(CC)CC)C.Cl[C:35](OC1C=CC([N+]([O-])=O)=CC=1)=[O:36].Cl.Cl.[NH:49]1[CH2:54][CH2:53][CH:52]([N:55]2[C:63]3[C:58](=[N:59][CH:60]=[CH:61][CH:62]=3)[NH:57][C:56]2=[O:64])[CH2:51][CH2:50]1>C(=O)([O-])[O-].[Na+].[Na+]>[Cl:1][C:2]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]2[CH2:11][N:12]3[C:19]([C:20]4([C:23]([F:24])([F:25])[F:26])[CH2:21][CH2:22]4)=[CH:18][N:17]=[C:13]3[C@H:14]([NH:16][C:35]([N:49]3[CH2:50][CH2:51][CH:52]([N:55]4[C:63]5[C:58](=[N:59][CH:60]=[CH:61][CH:62]=5)[NH:57][C:56]4=[O:64])[CH2:53][CH2:54]3)=[O:36])[CH2:15][C:4]=2[CH:3]=1

Komponenten

6

Edukt 4

HCID 8471Triethylamine2×HCID 821294-Nitrophenyl chloroformateHCID 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochlorideHCID 68781893HCID 68781893, Verbindung

Produkt 1

HCID 44200596HCID 44200596, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 10340Sodium CarbonateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To solution of (7R)-4-chloro-10-[1-(trifluoromethyl)cyclopropyl]-3,6,7,12-tetrahydroimidazo[1′,2′:1,7]azepino[3,4-e]indazol-7-amine (100 mg, 0.3 mmol) and triethyl amine (120 uL, 0.9 mmole) is added 4-nitrophenyl chloroformate (60 mg, 0.3 mmol) and stirred at 0° C. for 1 hr. 1-Piperidin-4-yl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one dihydrochloride [Burgey et al. WO 2006/044504], (87 mg, 0.3 mmol), is added along with triethylamine (120 uL, 0.9 mmol) and the reaction mixture is stirred at ambient temperature for 18 h. Saturated aqueous sodium carbonate (50 mL) is added and the mixture is extracted with dichloromethane (3×25 mL) The combined organic layers are washed with saturated aqueous sodium bicarbonate, brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography [100% dichloromethane→93% dichloromethane/methanol] provides the title compound.

Aufarbeitung

  1. stirringthe reaction mixture is stirred at ambient temperature for 18 h
  2. extractionthe mixture is extracted with dichloromethane (3×25 mL) The combined organic layers
  3. washare washed with saturated aqueous sodium bicarbonate, brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography [100% dichloromethane→93% dichloromethane/methanol]

Quellen und Nachweise

ORD-Eintrag
ord-ddd8d990a9c34ce182487dd7fea32861
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08796260B2

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