Potassium Carbonate → (6-Benzyl-2-chloro-pyrimidin-4-yl)-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine

HRID 1855397Notes

Reaction equation

HRID 1855397 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[CH3:26][O:27][C:28]1[CH:29]=[C:30]([NH2:40])[CH:31]=[CH:32][C:33]=1[N:34]1[CH:38]=[C:37]([CH3:39])[N:36]=[CH:35]1.[CH2:41]([C:48]1[CH:53]=[C:52](Cl)[N:51]=[C:50]([Cl:55])[N:49]=1)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:41]([C:48]1[N:49]=[C:50]([Cl:55])[N:51]=[C:52]([NH:40][C:30]2[CH:31]=[CH:32][C:33]([N:34]3[CH:38]=[C:37]([CH3:39])[N:36]=[CH:35]3)=[C:28]([O:27][CH3:26])[CH:29]=2)[CH:53]=1)[C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 454801813-methoxy-4-(4-methyl-1H-imidazol-1-yl)anilineHCID 462230714-Benzyl-2,6-dichloropyrimidine

Product 1

HCID 44192794(6-Benzyl-2-chloro-pyrimidin-4-yl)-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amineYield 24%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
20 °C

Procedure

Palladium acetate (2.7 mg, 0.012 mmol) and 2-(dicyclohexylphosphino)-biphenyl (8.5 mg, 0.024 mmol) were dissolved under an atmosphere of nitrogen under stirring in dioxane (1 mL). After 10 min stirring this solution was added to a suspension of 3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamine (61 mg, 0.3 mmol), 4-benzyl-2,6-dichloropyrimidine (71.7 mg, 0.3 mmol) and potassium carbonate (829 mg, 6 mmol) in dioxane (1.7 mL). The reaction was heated to reflux for 16 h. After cooling to 20° C. the reaction was poured onto water and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using dichloromethane/methanol (19:1 v/v) as eluent to yield the title compound (9.0 mg, 24%) as a yellow solid.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 16 h
  3. additionwas poured onto water
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-ad3398dace63476ea06407cda7af3d80
Source dataset
uspto-grants-2015_02
Patent number
US08962834B2

Reaction notes

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