Potassium Carbonate → 6-(3-Aminophenoxy)-5-(4-phenoxyphenyl)pyrimidin-4-amine

HRID 1522088Notes

Reaction equation

HRID 1522088 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[O:5][C:6]1[N:11]=[CH:10][N:9]=[C:8]([NH2:12])[C:7]=1Cl.[O:17]([C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[K+].[K+].[O-]S([O-])(=O)=O.[Na+].[Na+]>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[O:5][C:6]1[N:11]=[CH:10][N:9]=[C:8]([NH2:12])[C:7]=1[C:27]1[CH:28]=[CH:29][C:24]([O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:25][CH:26]=1

Participants

9

Reactant 5

HCID 11430Potassium CarbonateHCID 24436Sodium SulfateHCID 27343774-Phenoxyphenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 867217346-(3-Aminophenoxy)-5-chloropyrimidin-4-amine

Product 1

HCID 867217356-(3-Aminophenoxy)-5-(4-phenoxyphenyl)pyrimidin-4-amineYield 74%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Into a 20-mL microwave vial was placed 6-(3-aminophenoxy)-5-chloropyrimidin-4-amine (400.00 mg; 1.69 mmol.), (4-phenoxyphenyl)boronic acid (542.62 mg; 2.54 mmol), palladium acetate (18.97 mg; 0.08 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (69.39 mg; 0.17 mmol), potassium carbonate (700.77 mg; 5.07 mmol) suspended in dioxane (8.00 ml) and water (0.80 ml). The reaction mixture was run in the microwave for 20 minutes at 140° C. The reaction mixture was allowed to cool to rt. Na2SO4 was added to the mixture which was subsequently filtered through a plug of silica gel and concentrated under reduced pressure. The crude mixture was purified using Biotage column chromatography eluting from 80-100% EtOAc/hexanes, then 0-100% MeOH/EtOAc. Fractions containing the desired product were combined and concentrated under reduced pressure. The residue was lyophilized overnight to afford 6-(3-aminophenoxy)-5-(4-phenoxyphenyl)pyrimidin-4-amine as a yellow solid (177.00 mg, 74% yield).

Workup

  1. filtrationwas subsequently filtered through a plug of silica gel
  2. concentrationconcentrated under reduced pressure
  3. customThe crude mixture was purified
  4. washeluting from 80-100% EtOAc/hexanes
  5. additionFractions containing the desired product
  6. concentrationconcentrated under reduced pressure
  7. waitThe residue was lyophilized overnight

Sources & evidence

ORD record
ord-723f3f697db9420ebdb62b70f07166cb
Source dataset
uspto-grants-2015_07
Patent number
US09073947B2

Reaction notes

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