Piperazine → HCID 68467930, compound

HRID 1726330Notes

Reaction equation

HRID 1726330 reaction equation
C1(P(C2CCCCC2)C2C=CC=C[C:9]=2[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2N(C)C)CCCCC1.C(=O)([O-])[O-:30].[Cs+].[Cs+].I[C:36]1[CH:41]=[C:40]([CH2:42][N:43]2[CH:47]=[CH:46][CH:45]=[N:44]2)[CH:39]=[CH:38][C:37]=1[CH:48]=[CH:49][C:50]([OH:52])=[O:51].[NH:53]1[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1.O1CCO[CH2:61][CH2:60]1>C(O)(C)(C)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].O>[CH2:60]([O:52][C:50](=[O:51])[CH:49]=[CH:48][C:37]1[CH:38]=[CH:39][C:40]([CH2:42][N:43]2[CH:47]=[CH:46][CH:45]=[N:44]2)=[CH:41][C:36]=1[N:53]1[CH2:58][CH2:57][N:56]([C:9](=[O:30])[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:55][CH2:54]1)[CH3:61]

Participants

9

Reactant 5

HCID 4837PiperazineHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 68465963HCID 68465963, compound

Product 1

HCID 68467930HCID 68467930, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of tris(dibenzylideneacetone)dipalladium(0) (60 mg) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl(48 mg) in dioxane (3 ml) and t-butanol (3 ml) were added cesium carbonate (598 mg), 3-(2-iodo-4-(pyrazol-1-ylmethyl)phenyl)propenoic acid (500 mg) and piperazine (226 mg) under an atmosphere of argon and the mixture was stirred at 100° C. for 5 hours. To the reaction mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was extracted with 1N hydrochloric acid. The aqueous layer was neutralized with 1N aqueous solution of sodium hydroxide and then extracted with ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue was dissolved in methylene chloride (2 ml) under an atmosphere of argon. To the mixture were added benzoylchloride (0.15 ml) and pyridine (0.4 ml) and the mixture was stirred at room temperature for 2 hours. To the reaction solution was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by column chromatography on silica gel to give the title compound (306 mg) having the following physical data.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. extractionThe organic layer was extracted with 1N hydrochloric acid
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with water
  5. dry with materiala saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in methylene chloride (2 ml) under an atmosphere of argon
  8. additionTo the mixture were added benzoylchloride (0.15 ml) and pyridine (0.4 ml)
  9. stirringthe mixture was stirred at room temperature for 2 hours
  10. additionTo the reaction solution was added water
  11. extractionthe mixture was extracted with ethyl acetate
  12. washThe organic layer was washed with water
  13. dry with materiala saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate
  14. concentrationconcentrated
  15. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-a959091beb924a8a9f10751054b36721
Source dataset
uspto-grants-2009_02
Patent number
US07491748B2

Reaction notes

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