Toluene → (cis) (4-(4-Chloroindolin-1-yl)thiazol-2-yl) (2,6-dimethylmorpholino) methanone

HRID 1051883

Reaktionsgleichung

Reaktionsgleichung von HRID 1051883
Br[C:2]1[N:3]=[C:4]([C:7]([N:9]2[CH2:14][C@@H:13]([CH3:15])[O:12][C@@H:11]([CH3:16])[CH2:10]2)=[O:8])[S:5][CH:6]=1.[Cl:17][C:18]1[CH:26]=[CH:25][CH:24]=[C:23]2[C:19]=1[CH2:20][CH2:21][NH:22]2.C1(C)C=CC=CC=1.CC(C)([O-])C.[Na+]>C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:17][C:18]1[CH:26]=[CH:25][CH:24]=[C:23]2[C:19]=1[CH2:20][CH2:21][N:22]2[C:2]1[N:3]=[C:4]([C:7]([N:9]2[CH2:14][C@@H:13]([CH3:15])[O:12][C@@H:11]([CH3:16])[CH2:10]2)=[O:8])[S:5][CH:6]=1

Komponenten

7

Edukt 4

HCID 1140TolueneHCID 30163064-ChloroindolineHCID 23676156Sodium t-butoxideHCID 118444688(cis) (4-Bromothiazol-2-yl) (2,6-dimethylmorpholino)methanone2×

Produkt 1

HCID 118444685(cis) (4-(4-Chloroindolin-1-yl)thiazol-2-yl) (2,6-dimethylmorpholino) methanoneAusbeute 60,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

(cis) (4-bromothiazol-2-yl) (2,6-dimethylmorpholino)methanone (step-1 of compound 45, 1.0 g, 3.28 mmol) and 4-chloroindoline (0.55 g, 3.60 mmol) were added to seal tube containing toluene (25 ml). Sodium tert-butoxide (0.47 g. 4.91 mmol) was added, the nitrogen gas was bubbled through reaction mixture for 15 minutes and tris(dibenzylideneacetone)dipalladium(0) (0.15 g, 0.16 mmol) was added under nitrogen and the tube was sealed. The reaction mixture was heated at 100° C. for 18 hr under stirring. The progress of reaction was monitored by TLC. The reaction mixture was cooled to 25° C. and diluted with ethyl acetate (100 ml) and washed with water (25 ml). The organic layer was dried over sodium sulfate filtered and concentrated under reduced pressure to obtain a crude product; which was purified by flash column chromatography using 15% ethyl acetate in hexanes as an eluent to obtain the title compound (0.75 g, 60.6%). MS: m/z 378 (M+1).

Aufarbeitung

  1. customto seal tube
  2. customthe nitrogen gas was bubbled through reaction mixture for 15 minutes
  3. customthe tube was sealed
  4. customThe progress of reaction
  5. temperatureThe reaction mixture was cooled to 25° C.
  6. washwashed with water (25 ml)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto obtain a crude product
  11. customwhich was purified by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-3261e83e92d849728003b467ffd60899
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09388196B2

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