Cesium carbonate → ethyl 1-phenyl-5-(phenylamino)-1H-pyrazole-3-carboxylate

HRID 2194706Notes

Reaction equation

HRID 2194706 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[C:4]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:3]=1.I[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.O1CCCC1.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(OCC)(=O)C.O>[C:7]1([N:6]2[C:2]([NH:1][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:3][C:4]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[N:5]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

10

Reactant 4

HCID 10796Cesium carbonateHCID 11575IodobenzeneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23630921Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate

Product 1

HCID 68410675ethyl 1-phenyl-5-(phenylamino)-1H-pyrazole-3-carboxylateYield 59%

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate (443 mg) synthesized according to the method described in WO2004/98589, iodobenzene (469 mg), cesium carbonate (1.2 g), tris(dibenzylideneacetone)dipalladium (0) (87 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (111 mg) were suspended in toluene (10 mL) and tetrahydrofuran (2 mL), and the mixture was sufficiently deaerated, and stirred at 120° C. for 18 hr under an argon atmosphere. The reaction mixture was allowed to cool to room temperature, water and ethyl acetate were added, and the mixture was filtered through celite. The organic layer of the filtrate was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate=7:1→3:1), and the obtained solid was washed with a mixed solvent of diisopropyl ether and ethyl acetate to give the title compound as a pale-red solid (yield 345 mg, yield 59%).

Workup

  1. temperatureto cool to room temperature
  2. filtrationthe mixture was filtered through celite
  3. washThe organic layer of the filtrate was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate=7:1→3:1)
  7. washthe obtained solid was washed with a mixed solvent of diisopropyl ether and ethyl acetate

Sources & evidence

ORD record
ord-d7d949d52824457a8065cb5e86105f2a
Source dataset
uspto-grants-2012_12
Patent number
US08334301B2

Reaction notes

Loading…