Toluene → 1-[5-(4-Fluoro phenyl)-2-methyl-thiazol-4-yl]-1-{(S)-2-[(5-trifluoromethyl-pyrimidin-2-ylamino)-methyl]-pyrrolidin-1-yl}-methanone

HRID 2074411

Reaktionsgleichung

Reaktionsgleichung von HRID 2074411
Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([C:17]2[N:18]=[C:19]([CH3:29])[S:20][C:21]=2[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)=[O:16])=[N:6][CH:7]=1.[F:30][C:31]([F:36])([F:35])C([O-])=O.[K+].C1(C)C=CC=CC=1.O.CCOCC>CN(C)C=O.[Cu](I)I>[F:28][C:25]1[CH:26]=[CH:27][C:22]([C:21]2[S:20][C:19]([CH3:29])=[N:18][C:17]=2[C:15]([N:11]2[CH2:12][CH2:13][CH2:14][C@H:10]2[CH2:9][NH:8][C:5]2[N:4]=[CH:3][C:2]([C:31]([F:36])([F:35])[F:30])=[CH:7][N:6]=2)=[O:16])=[CH:23][CH:24]=1

Komponenten

7

Edukt 4

HCID 1140TolueneHCID 21584184Diethylether waterHCID 23662811Potassium trifluoroacetateHCID 670897411-{(S)-2-[(5-Bromo-pyrimidin-2-ylamino)methyl]-pyrrolidin-1-yl}-1-[5-(4-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone

Produkt 1

HCID 670903201-[5-(4-Fluoro phenyl)-2-methyl-thiazol-4-yl]-1-{(S)-2-[(5-trifluoromethyl-pyrimidin-2-ylamino)-methyl]-pyrrolidin-1-yl}-methanoneAusbeute 0,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 83717Copper iodideKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To the compound from Example 194 (0.36 g) in dimethylformamide (5 ml) was added potassium trifluoroacetate (0.23 g), copper iodide (0.3 g) and toluene (5 ml) and the resulting mixture heated at reflux under Dean-Stark conditions for 3 h, before refluxing for a further 20 h. The reaction mixture was cooled, poured into water/ether and filtered through kieselguhr. The aqueous layer from the filtrate was extracted with ether, and the combined ether extracts washed with water, dried and evaporated. The aqueous was re-extracted with dichloromethane and the extract evaporated. The combined extracts were chromatographed on silica gel, eluting with methanol-dichloromethane mixtures, to afford the title product (0.001 g). Mass Spectrum (Electrospray LC/MS): Found 466 (MH+). C21H19F4N5OS requires 465.

Aufarbeitung

  1. temperaturethe resulting mixture heated
  2. temperatureat reflux under Dean-Stark conditions for 3 h
  3. temperaturebefore refluxing for a further 20 h
  4. temperatureThe reaction mixture was cooled
  5. filtrationfiltered through kieselguhr
  6. extractionThe aqueous layer from the filtrate was extracted with ether
  7. washthe combined ether extracts washed with water
  8. customdried
  9. customevaporated
  10. extractionThe aqueous was re-extracted with dichloromethane
  11. customthe extract evaporated
  12. customThe combined extracts were chromatographed on silica gel
  13. washeluting with methanol-dichloromethane mixtures

Quellen und Nachweise

ORD-Eintrag
ord-6b1883a0edd0425f9d7085d49b94a564
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07919507B2

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