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

HRID 1051883

Reaction equation

HRID 1051883 reaction equation
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

Participants

7

Reactant 4

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

Product 1

HCID 118444685(cis) (4-(4-Chloroindolin-1-yl)thiazol-2-yl) (2,6-dimethylmorpholino) methanoneYield 60.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

(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).

Workup

  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

Sources & evidence

ORD record
ord-3261e83e92d849728003b467ffd60899
Source dataset
uspto-grants-2016_07
Patent number
US09388196B2

Linked notes

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