Sodium Carbonate → 4-Chloro-6-(5-chloro-2-methylphenyl)pyrimidin-2-yl-amine

HRID 28538

Reaktionsgleichung

Reaktionsgleichung von HRID 28538
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:12]=[CH:13][C:14]([CH3:20])=[C:15](B(O)O)[CH:16]=1.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.CC(C)=O.C(COC)OC>[Cl:8][C:6]1[CH:7]=[C:2]([C:13]2[CH:12]=[C:11]([Cl:10])[CH:16]=[CH:15][C:14]=2[CH3:20])[N:3]=[C:4]([NH2:9])[N:5]=1

Komponenten

9

Edukt 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 655222-Amino-4,6-dichloropyrimidineHCID 2773336(5-Chloro-2-methylphenyl)boronic acid

Produkt 1

HCID 860043474-Chloro-6-(5-chloro-2-methylphenyl)pyrimidin-2-yl-amineAusbeute 40,3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 167845palladium(II) acetateKatalysatorHCID 180AcetoneLösungsmittelHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

To a mixture of 4,6-dichloro-2-amino-pyrimidine (0.481 g, 2.93 mmol), 5-chloro-2-methyl-phenyl boronic acid (0.5 g, 2.93 mmol), palladium (II) acetate (0.1 g, 0.44 mmol), and triphenylphosphine (0.23 g, 0.88 mmol) was added a solution of sodium carbonate (1.5 g, 14.6 mmol) in water (5.0 ml) followed by glyme (20 ml). The mixture was stirred under an argon atmosphere for 16 hours. After addition of acetone (15 ml), the mixture was filtered through a pad of celite under suction and the filtrate was concentrated under vacuum. The residual solid was purified by flash chromatography on silica gel eluting with ethyl acetate-hexane (1:9). After concentration under reduced pressure, the solid was dissolved in methanol and a solution of hydrogen chloride in dioxane (4.0 M, 5 ml) was added. After concentration under vacuum, the solid was treated with ethyl acetate (5 ml) and stirred for one hour. Filtration provided the hydrochloride salt of 4-chloro-6-(5-chloro-2-methyl-phenyl) pyrimidin-2-yl-amine (0.30 g, 35% yield) as a white powder.

Aufarbeitung

  1. filtrationthe mixture was filtered through a pad of celite under suction
  2. concentrationthe filtrate was concentrated under vacuum
  3. customThe residual solid was purified by flash chromatography on silica gel eluting with ethyl acetate-hexane (1:9)
  4. concentrationAfter concentration under reduced pressure
  5. dissolutionthe solid was dissolved in methanol
  6. additiona solution of hydrogen chloride in dioxane (4.0 M, 5 ml) was added
  7. concentrationAfter concentration under vacuum
  8. additionthe solid was treated with ethyl acetate (5 ml)
  9. stirringstirred for one hour
  10. filtrationFiltration

Quellen und Nachweise

ORD-Eintrag
ord-52d60904d655427e82e02ae00f5b1749
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07419984B2

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