Bromobenzene → [4-(5-Methyl-3-phenyl-isoxazol-4-yl)-pyrimidin-2-yl]-phenyl-amine

HRID 2120854Notes

Reaction equation

HRID 2120854 reaction equation
[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[N:14]=1.Br[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:3]=1[C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:14]=1

Participants

8

Reactant 4

HCID 7961BromobenzeneHCID 634876Binap, (A+-)-HCID 27457214-(5-Methyl-3-phenylisoxazol-4-yl)pyrimidin-2-amineHCID 23676156Sodium t-butoxide

Product 1

HCID 9949334[4-(5-Methyl-3-phenyl-isoxazol-4-yl)-pyrimidin-2-yl]-phenyl-amineYield 36.5%

Reagents, catalysts & solvents 3

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 50 mg (0.2 mmol) of 4-(5-methyl-3-phenyl-isoxazole-4-yl)-pyrimidin-2-ylamine in 1 mL of toluene was added successively 63 μL (0.6 mmol) of bromobenzene, 10 mg of tris(dibenzylideneacetone) dipalladium, 10 mg of BINAP and 39 mg (0.4 mmol) of sodium tert-butoxide. The mixture was heated at reflux for 16 h, diluted with ethyl acetate, filtered, washed successively with saturated aqueous sodium bicarbonate and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography over silica gel eluted with ethyl acetate-hexanes 1:3, to afford 24 mg (36%) of the title compound as a yellow oil.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 16 h
  3. filtrationfiltered
  4. washwashed successively with saturated aqueous sodium bicarbonate and brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography over silica gel
  8. washeluted with ethyl acetate-hexanes 1:3

Sources & evidence

ORD record
ord-083f390df6c944ada4fb5972d6ac3784
Source dataset
uspto-grants-2004_02
Patent number
US06693108B2

Reaction notes

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