Sodium Carbonate → 4-Chloro-6-(2,5-dichloro-phenyl)-pyrimidin-2-yl-amine

HRID 28536

Reaction equation

HRID 28536 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([NH2:9])[N:3]=1.[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1B(O)O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(COC)OC>[Cl:8][C:6]1[CH:7]=[C:2]([C:15]2[CH:16]=[C:11]([Cl:10])[CH:12]=[CH:13][C:14]=2[Cl:17])[N:3]=[C:4]([NH2:9])[N:5]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 655222-Amino-4,6-dichloropyrimidineHCID 27733712,5-Dichlorobenzeneboronic acid

Product 1

HCID 865945994-Chloro-6-(2,5-dichloro-phenyl)-pyrimidin-2-yl-amineYield 31.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixture of 4,6-dichloro-pyrimidin-2-yl-amine (0.625 g, 3.81 mmol), 2,5-dichloro-phenyl boronic acid (0.726 g, 3.81 mmol), palladium (II) acetate (0.128 g, 0.57 mmol) and triphenylphosphine (0.30 g, 1.14 mmol) was added a solution of sodium carbonate (2.0 g, 19.0 mmol) in water (5 ml) followed by glyme (20 ml). The mixture was stirred under an argon atmosphere for 6 hours. Filtration and concentration of the filtrate yielded the crude product which was purified by flash chromatography on silica gel eluting with ethyl acetate-chloroform (1:8). After evaporation of solvents under reduced pressure, the residue was dissolved in ethanol (100 ml) and stirred while a solution of hydrogen chloride in dioxane (4.0 M, 2.5 ml) was added. After evaporation of volatiles under reduced pressure, the residue was treated with ethyl acetate (25 ml) and stirred for 16 hours. Filtration provided the hydrochloride salt of 4-chloro-6-(2,5-dichloro-phenyl)-pyrimidin-2-yl-amine (0.330 g, 28% yield) as a white powder.

Workup

  1. filtrationFiltration and concentration of the filtrate
  2. customyielded the crude product which
  3. customwas purified by flash chromatography on silica gel eluting with ethyl acetate-chloroform (1:8)
  4. customAfter evaporation of solvents under reduced pressure
  5. dissolutionthe residue was dissolved in ethanol (100 ml)
  6. stirringstirred while a solution of hydrogen chloride in dioxane (4.0 M, 2.5 ml)
  7. additionwas added
  8. customAfter evaporation of volatiles under reduced pressure
  9. additionthe residue was treated with ethyl acetate (25 ml)
  10. stirringstirred for 16 hours
  11. filtrationFiltration

Sources & evidence

ORD record
ord-2531632c8b87439aa6a3f8e3c1770705
Source dataset
uspto-grants-2008_09
Patent number
US07419984B2

Linked notes

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