Water → TAK-632

HRID 455243Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 455243
[NH2:1][C:2]1[S:3][C:4]2[C:10]([C:11]#[N:12])=[C:9]([O:13][C:14]3[CH:15]=[CH:16][C:17]([F:34])=[C:18]([NH:20][C:21](=[O:33])[CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=4)[CH:19]=3)[CH:8]=[CH:7][C:5]=2[N:6]=1.N1C=CC=CC=1.[CH:41]1([C:44](Cl)=[O:45])[CH2:43][CH2:42]1.O>CN(C)C(=O)C>[C:11]([C:10]1[C:4]2[S:3][C:2]([NH:1][C:44]([CH:41]3[CH2:43][CH2:42]3)=[O:45])=[N:6][C:5]=2[CH:7]=[CH:8][C:9]=1[O:13][C:14]1[CH:15]=[CH:16][C:17]([F:34])=[C:18]([NH:20][C:21](=[O:33])[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:30])[F:31])[CH:24]=2)[CH:19]=1)#[N:12]

Komponenten

6

Edukt 4

HCID 962WaterHCID 1049PyridineHCID 77637Cyclopropanecarbonyl chloride2×HCID 86644708HCID 86644708, Verbindung

Produkt 1

HCID 46209401TAK-632Ausbeute 95,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

To a solution of N-{5-[(2-amino-7-cyano-1,3-benzothiazol-6-yl)oxy]-2-fluorophenyl}-2-[3-(trifluoromethyl)phenyl]acetamide (980 mg, 2.01 mmol) in N,N-dimethylacetamide (8 mL) were added pyridine (242 μL, 3.02 mmol) and cyclopropanecarbonyl chloride (255 μL, 2.81 mmol), and the mixture was stirred at room temperature for 2 hr. Cyclopropanecarbonyl chloride (255 μL, 2.81 mmol) was added to the reaction mixture, and the mixture was further stirred at room temperature for 2 hr. Water (20 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution (20 mL) and saturated brine (20 mL), and dried over anhydrous magnesium sulfate. Insoluble material was filtered off, the filtrate was purified by basic silica gel column chromatography (eluate: ethyl acetate), and the obtained solution was concentrated under reduced pressure. A pale-brown oil residue was crystallized from ethanol/water (1/1) to give the title compound (1.06 g, 95%) as a white powder.

Aufarbeitung

  1. stirringthe mixture was further stirred at room temperature for 2 hr
  2. extractionthe mixture was extracted with ethyl acetate (20 mL)
  3. washThe organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution (20 mL) and saturated brine (20 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationInsoluble material was filtered off
  6. customthe filtrate was purified by basic silica gel column chromatography (eluate: ethyl acetate)
  7. concentrationthe obtained solution was concentrated under reduced pressure
  8. customA pale-brown oil residue was crystallized from ethanol/water (1/1)

Quellen und Nachweise

ORD-Eintrag
ord-6d242aac376845f9b0f45a087cb8514f
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08497274B2

Notizen zur Reaktion

Wird geladen…