Water → HCID 117678157, Verbindung

HRID 1778174Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1778174
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12](Cl)[N:11]=[C:10]([N:15]3[CH2:20][C@@H:19]4[CH2:21][C@H:16]3[CH2:17][N:18]4[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH:9]=2)=[CH:4][C:3]=1[C:29]([F:32])([F:31])[F:30].Cl.[CH:34]12[CH2:39][CH:37]([CH2:38]1)[CH2:36][NH:35]2.C(=O)([O-])[O-].[K+].[K+].O>CS(C)=O>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([N:35]3[CH2:36][CH:37]4[CH2:39][CH:34]3[CH2:38]4)[N:11]=[C:10]([N:15]3[CH2:20][C@@H:19]4[CH2:21][C@H:16]3[CH2:17][N:18]4[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH:9]=2)=[CH:4][C:3]=1[C:29]([F:32])([F:31])[F:30]

Komponenten

6

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 552197462-Azabicyclo(2.1.1)hexane hydrochlorideHCID 117678278(1S,4S)-tert-butyl 5-(6-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-2-chloropyrimidin-4-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

Produkt 1

HCID 117678157HCID 117678157, VerbindungAusbeute 53,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a solution of (1S,4S)-tert-butyl 5-(6-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-2-chloropyrimidin-4-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (220 mg, 0.47 mmol) in DMSO (2 mL) was added 2-azabicyclo[2.1.1]hexane hydrochloride (68 mg, 0.56 mmol) and potassium carbonate (130 mg, 0.93 mmol). The mixture was heated at 90° C. for 16 h. After cooling to room temperature, water (50 mL) was added to. The mixture was extracted with ethyl acetate (30 mL (3 times)). The organic layer was dried over sodium sulfate, concentrated and purified by flash column chromatography (50% ethyl acetate in petroleum ether to 100% ethyl acetate) to provide (1S,4S)-tert-butyl 5-(6-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-2-(2-azabicyclo[2.1.1]hexan-2-yl)pyrimidin-4-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (130 mg, 53.7% yield). LCMS (ESI): [MH]+=518.0.

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (30 mL (3 times))
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (50% ethyl acetate in petroleum ether to 100% ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-0daa0c3e93554917aa07e05728cf66b9
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09266862B2

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