Hydrochloric Acid → 2-Chloro-6-(5-chloro-2-methoxy-phenyl)-pyrimidin-4-yl-amine

HRID 28548

Reaction equation

HRID 28548 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[C:4](Cl)[N:3]=1.[Cl:10][C:11]1[CH:12]=[CH:13][C:14]([O:20][CH3:21])=[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+].Cl>O.C(O)C.O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(Cl)(Cl)Cl.CC(C)=O.C(COC)OC>[Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[C:4]([C:13]2[CH:12]=[C:11]([Cl:10])[CH:16]=[CH:15][C:14]=2[O:20][CH3:21])[N:3]=1

Participants

13

Reactant 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 823874-Pyrimidinamine, 2,6-dichloro-HCID 27357515-Chloro-2-methoxyphenylboronic acid

Product 1

HCID 865946002-Chloro-6-(5-chloro-2-methoxy-phenyl)-pyrimidin-4-yl-amineYield 15.5%

Reagents, catalysts & solvents 7

HCID 167845palladium(II) acetateCatalystHCID 180AcetoneSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 6212ChloroformSolventHCID 80711,2-DimethoxyethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

Alternatively, to a mixture of 2,6-dichloro-pyrimidin-4-yl-amine (1.64 g, 10.0 mmol), 5-chloro-2-methoxy-phenyl boronic acid (1.84 g, 10.0 mmol), palladium (II) acetate (0.337 g, 1.0 mmol) and triphenylphosphine (0.786 g, 3.0 mmol) was added a solution of sodium carbonate (5.3 g, 50.0 mmol) in water (10 ml) followed by glyme (50 ml). The mixture was stirred under an argon atmosphere for 24 hours. After addition of acetone (50 ml), filtration and concentration of the filtrate provided the crude product which was treated with chloroform (50 ml) and stirred for 1 hour. Filtration provided a solid which was dissolved in ethanol (50 ml). A solution of hydrogen chloride in dioxane (4.0 M, 5 ml) was added and volatiles were evaporated under reduce pressure. The residue was treated with ethyl acetate (25 ml) and stirred for 2 hours. Filtration provided the hydrochloride salt of 2-chloro-6-(5-chloro-2-methoxy-phenyl)-pyrimidin-4-yl-amine (0.42 g, 14% yield).

Workup

  1. customprovided the crude product which
  2. stirringstirred for 1 hour
  3. filtrationFiltration
  4. customprovided a solid which
  5. customvolatiles were evaporated
  6. additionThe residue was treated with ethyl acetate (25 ml)
  7. stirringstirred for 2 hours
  8. filtrationFiltration

Sources & evidence

ORD record
ord-110455df7da74eaf8850a0a690f33539
Source dataset
uspto-grants-2008_09
Patent number
US07419984B2

Linked notes

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