Cesium carbonate → cis-1-Acetyl-6-(3,5-dimethylpiperazin-1-yl)-5-methoxyindoline

HRID 2214752Notes

Reaction equation

HRID 2214752 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:53]([N:56]1[C:64]2[C:59](=[CH:60][C:61]([O:66][CH3:67])=[C:62](Br)[CH:63]=2)[CH2:58][CH2:57]1)(=[O:55])[CH3:54].[CH3:68][C@H:69]1[CH2:74][NH:73][CH2:72][C@@H:71]([CH3:75])[NH:70]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:53]([N:56]1[C:64]2[C:59](=[CH:60][C:61]([O:66][CH3:67])=[C:62]([N:73]3[CH2:72][C@H:71]([CH3:75])[NH:70][C@H:69]([CH3:68])[CH2:74]3)[CH:63]=2)[CH2:58][CH2:57]1)(=[O:55])[CH3:54]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 6950261rel-(2R,6S)-2,6-dimethylpiperazineHCID 219483751-Acetyl-6-bromo-5-methoxyindoline

Product 1

HCID 69664906cis-1-Acetyl-6-(3,5-dimethylpiperazin-1-yl)-5-methoxyindolineYield 63.2%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

A mixture of palladium (II) acetate (830 mg, 3.7 mmole), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (3.46 g, 5.5 mmole) and cesium carbonate (18.1 g, 56 mmole) in dry degassed 1,4-dioxane (200 ml) under argon was sonicated at 28° C. for 0.5 h producing a pink heterogeneous mixture. This was treated with D1 (10 g, 37 mmole) followed by cis-2,6-dimethylpiperazine (12.6 g, 110 mmole) and heated with rapid stirring at reflux for 96 h. The mixture was allowed to cool, filtered through Kieselguhr and then concentrated under vacuum. The residue was treated with EtOAc and 2M HCl acid, shaken well and the aqueous layer separated, basified by addition of K2CO3 and extracted with DCM. The extract was dried (Na2SO4) and concentrated under vacuum to afford the title compound as a pale orange solid (7.1 g, 63%). MH+ 304.

Workup

  1. customin dry
  2. customdegassed 1,4-dioxane (200 ml) under argon
  3. customwas sonicated at 28° C. for 0.5 h
  4. customproducing a pink heterogeneous mixture
  5. temperatureheated
  6. temperatureat reflux for 96 h
  7. temperatureto cool
  8. filtrationfiltered through Kieselguhr
  9. concentrationconcentrated under vacuum
  10. additionThe residue was treated with EtOAc and 2M HCl acid
  11. stirringshaken well
  12. customthe aqueous layer separated
  13. additionbasified by addition of K2CO3
  14. extractionextracted with DCM
  15. dry with materialThe extract was dried (Na2SO4)
  16. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-c0694c3c82f34c59bff5cd6f16af9d04
Source dataset
uspto-grants-2006_09
Patent number
US07109201B2

Reaction notes

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