Sodium Carbonate → 4-Chloro-6-(2,3,5-trichloro-phenyl)-pyrimidin-2-yl-amine-hydrochloride salt

HRID 28639Notes

Reaction equation

HRID 28639 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([Cl:9])=[CH:4][C:3]=1B(O)O.[Cl:13][C:14]1[CH:19]=[C:18](Cl)[N:17]=[C:16]([NH2:21])[N:15]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>COCCOC.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC(C)=O>[ClH:1].[Cl:13][C:14]1[CH:19]=[C:18]([C:3]2[CH:4]=[C:5]([Cl:9])[CH:6]=[C:7]([Cl:8])[C:2]=2[Cl:1])[N:17]=[C:16]([NH2:21])[N:15]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 655222-Amino-4,6-dichloropyrimidineHCID 51065082,3,5-Trichlorophenylboronic acid

Product 1

HCID 876466484-Chloro-6-(2,3,5-trichloro-phenyl)-pyrimidin-2-yl-amine-hydrochloride saltYield 40.4%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 180AcetoneSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 2,3,5-trichloro-phenyl boronic acid (12 g, 53 mmol) and 4,6-dichloro-pyrimidin-2-yl-amine (10.5 g, 64 mmol) in ethylene glycol dimethyl ether (300 ml) under Argon atmosphere was stirred for 30 minutes. A mixture of palladium (II) acetate (1.8 g, 8 mmol), a solution of sodium carbonate (28.2 g, 270 mmol) in water (100 ml), and triphenylphosphine (4.2 g, 16 mmol) were added and the mixture was stirred for 18 hours. The mixture was treated with acetone (500 ml), filtered through a pad of celite under suction and concentrated under reduced pressure. The residue was treated with water (100 ml) and the mixture was stirred vigorously. The solid was filtered and dissolved in tetrahydrofuran (100 ml). Hydrogen chloride (4 M in dioxane, 20 ml) was added. After stirring for 1 hour, the solid was filtered and dried under reduced pressure. The solid was treated with ethyl acetate (50 ml) and stirred for 30 minutes. The solid was filtered and dried under reduced pressure to afford 4-chloro-6-(2,3,5-trichloro-phenyl)-pyrimidin-2-yl-amine-hydrochloride salt (3.7 g, 20% yield) as a white powder.

Workup

  1. stirringthe mixture was stirred for 18 hours
  2. filtrationfiltered through a pad of celite under suction
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue was treated with water (100 ml)
  5. stirringthe mixture was stirred vigorously
  6. filtrationThe solid was filtered
  7. dissolutiondissolved in tetrahydrofuran (100 ml)
  8. additionHydrogen chloride (4 M in dioxane, 20 ml) was added
  9. stirringAfter stirring for 1 hour
  10. filtrationthe solid was filtered
  11. customdried under reduced pressure
  12. additionThe solid was treated with ethyl acetate (50 ml)
  13. stirringstirred for 30 minutes
  14. filtrationThe solid was filtered
  15. customdried under reduced pressure

Sources & evidence

ORD record
ord-0925e98245224d7198554541457d5b6f
Source dataset
uspto-grants-2008_09
Patent number
US07419984B2

Reaction notes

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