Cesium carbonate → Ethyl 7-(4-(2-(1-acetylindolin-5-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxylate

HRID 383822

Reaction equation

HRID 383822 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.Br[C:42]1[C:50]2[O:49][C:48]([C:51]([O:53][CH2:54][CH3:55])=[O:52])=[CH:47][C:46]=2[CH:45]=[CH:44][CH:43]=1.[N:56]1([CH2:62][CH2:63][C:64]2[CH:65]=[C:66]3[C:70](=[CH:71][CH:72]=2)[N:69]([C:73](=[O:75])[CH3:74])[CH2:68][CH2:67]3)[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:73]([N:69]1[C:70]2[C:66](=[CH:65][C:64]([CH2:63][CH2:62][N:56]3[CH2:61][CH2:60][N:59]([C:42]4[C:50]5[O:49][C:48]([C:51]([O:53][CH2:54][CH3:55])=[O:52])=[CH:47][C:46]=5[CH:45]=[CH:44][CH:43]=4)[CH2:58][CH2:57]3)=[CH:72][CH:71]=2)[CH2:67][CH2:68]1)(=[O:75])[CH3:74]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 46738833Ethyl 7-bromobenzofuran-2-carboxylateHCID 596367471-(5-(2-(Piperazin-1-yl)ethyl)indolin-1-yl)ethanone

Product 1

HCID 59636756Ethyl 7-(4-(2-(1-acetylindolin-5-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxylateYield 61.5%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
95 °C

Procedure

Cesium carbonate (0.724 g, 2.22 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (0.081 g, 0.17 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.078 g, 0.09 mmol) were added under argon to a mixture of ethyl 7-bromobenzofuran-2-carboxylate (0.460 g, 1.71 mmol) and 1-(5-(2-(piperazin-1-yl)ethyl)indolin-1-yl)ethanone (0.491 g, 1.79 mmol) (example 38c) in dry degassed dioxane (8 mL) and the reaction was heated at 95° C. over night. After cooling to room temperature, water and DCM were added and the layers separated. The aq phase was extracted with DCM (3×). The combined organic phases were washed with water, dried (MgSO4), filtered and evaporated. The crude product was purified by flash chromatography (DCM/MeOH 95/5) to give 0.485 g (61%) of the product.

Workup

  1. customin dry
  2. customdegassed dioxane (8 mL)
  3. temperatureAfter cooling to room temperature
  4. additionwater and DCM were added
  5. customthe layers separated
  6. extractionThe aq phase was extracted with DCM (3×)
  7. washThe combined organic phases were washed with water
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product was purified by flash chromatography (DCM/MeOH 95/5)

Sources & evidence

ORD record
ord-2d5ff01034b24f9a9aa7cf399164cec2
Source dataset
uspto-grants-2013_02
Patent number
US08367676B2

Linked notes

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