Cesium carbonate → Tert-butyl 2-(2-(benzyloxy)-5-(4-methylpiperazin-1-yl)benzamido)-4-phenylbenzoate

HRID 454602Notes

Reaction equation

HRID 454602 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:14]([O:21][C:22]1[CH:49]=[CH:48][C:47](Br)=[CH:46][C:23]=1[C:24]([NH:26][C:27]1[CH:39]=[C:38]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:37]=[CH:36][C:28]=1[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:25])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=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([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C1(C)C=CC=CC=1>[CH2:14]([O:21][C:22]1[CH:49]=[CH:48][C:47]([N:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)=[CH:46][C:23]=1[C:24]([NH:26][C:27]1[CH:39]=[C:38]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:37]=[CH:36][C:28]=1[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:25])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonate2×HCID 531671-Methylpiperazine2×HCID 66990333Tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate

Product 1

HCID 66990034Tert-butyl 2-(2-(benzyloxy)-5-(4-methylpiperazin-1-yl)benzamido)-4-phenylbenzoate

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalyst2×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalyst2×HCID 1140TolueneSolvent

Procedure

1-Methylpiperazine (0.089 mL), cesium carbonate (0.35 g), tris(dibenzylideneacetone)dipalladium(0) (4.9 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (13 mg), and palladium(II) acetate (2.4 mg) were added to a toluene (4.5 mL) solution of tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate (0.30 g), followed by heating to reflux under a nitrogen atmosphere for 3 hours. The reaction mixture was cooled to room temperature, and then 1-methylpiperazine (0.060 mL), cesium carbonate (0.18 g), tris(dibenzylideneacetone)dipalladium(0) (4.9 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (13 mg), and palladium(II) acetate (2.4 mg) were added thereto, followed by heating to reflux under a nitrogen atmosphere for 3 hours. After cooling the reaction mixture to room temperature, the solvent was evaporated under reduced pressure, and water and chloroform were added to the residue. The insoluble substance was removed by filtration. The organic layer was separated, washed with a 1 mol/L aqueous solution of sodium hydroxide and a saturated aqueous solution of sodium chloride sequentially, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 100-90% chloroform/methanol] to obtain 0.26 g of tert-butyl 2-(2-(benzyloxy)-5-(4-methylpiperazin-1-yl)benzamido)-4-phenylbenzoate.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 3 hours
  3. temperatureby heating
  4. temperatureto reflux under a nitrogen atmosphere for 3 hours
  5. temperatureAfter cooling the reaction mixture to room temperature
  6. customthe solvent was evaporated under reduced pressure, and water and chloroform
  7. additionwere added to the residue
  8. customThe insoluble substance was removed by filtration
  9. customThe organic layer was separated
  10. washwashed with a 1 mol/L aqueous solution of sodium hydroxide
  11. dry with materiala saturated aqueous solution of sodium chloride sequentially, and dried over anhydrous magnesium sulfate
  12. customthe solvent was evaporated under reduced pressure
  13. customThe obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 100-90% chloroform/methanol]

Sources & evidence

ORD record
ord-8140d9f201ce4e819acf149f287b7fc6
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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