2,4-Dichloropyrimidine → N'-(4-((2-chloro-4-pyrimidinyl)oxy)phenyl)-N,N-dimethylurea

HRID 1414215Notes

Reaction equation

HRID 1414215 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:13])[N:10]([CH3:12])[CH3:11])=[CH:4][CH:3]=1.C[O-].[Na+].OC1C=CC(NC(=O)N(C)C)=CC=1.[Na].[Cl:31][C:32]1[N:37]=[C:36](Cl)[CH:35]=[CH:34][N:33]=1>CS(C)=O.CO>[Cl:31][C:32]1[N:37]=[C:36]([O:1][C:2]2[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:13])[N:10]([CH3:11])[CH3:12])=[CH:6][CH:7]=2)[CH:35]=[CH:34][N:33]=1

Participants

7

Reactant 4

HCID 775312,4-DichloropyrimidineHCID 3014146Urea, N'-(4-hydroxyphenyl)-N,N-dimethyl-HCID 10942334Sodium MethoxideHCID 68122779sodium 4-hydroxyphenyl-N,N-dimethylurea

Product 1

HCID 21486802N'-(4-((2-chloro-4-pyrimidinyl)oxy)phenyl)-N,N-dimethylurea

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Procedure

4-Hydroxyphenyl-N,N-dimethylurea (12.0 grams; 0.066 mole) was mixed with a solution of sodium methylate (prepared by mixing sodium metal (1.53 grams) in 55 milliliters (ml) of methanol) and the resulting sodium 4-hydroxyphenyl-N,N-dimethylurea solution added gradually over a period of about one hour to a solution of 2,4-dichloropyrimidine (9.94 grams; 0.066 mole) in 50 ml. of dimethylsulfoxide. During the addition, the reaction temperature rose from about 55°C. to a temperature from between about 60° to about 65°C. The resulting reaction mixture was maintained at temperatures from between about 60° to about 70°C. for a period of about 30 minutes. The reaction mixture, which was nearly neutral, was poured into about 300 ml. of cold water and the resulting product precipitate recovered by filtration and washed with additional portions of water. The product precipitate was dissolved in acetonitrile and the resulting solution filtered with activated charcoal and then cooled to crystallize the product. The product thus obtained was recrystallized again from methylene chloride and dried. As a result of these operations, the desired title product was obtained as a white solid having a melting point of 192°C.

Workup

  1. additionDuring the addition
  2. customrose from about 55°C. to a temperature from between about 60° to about 65°C
  3. customThe resulting reaction mixture
  4. temperaturewas maintained at temperatures from between about 60° to about 70°C. for a period of about 30 minutes
  5. additionwas poured into about 300 ml
  6. filtrationof cold water and the resulting product precipitate recovered by filtration
  7. washwashed with additional portions of water
  8. dissolutionThe product precipitate was dissolved in acetonitrile
  9. filtrationthe resulting solution filtered with activated charcoal
  10. temperaturecooled
  11. customto crystallize the product
  12. customThe product thus obtained
  13. customwas recrystallized again from methylene chloride
  14. customdried
  15. customAs a result of these operations

Sources & evidence

ORD record
ord-8ba1cf1230cb492a8ef81e17a393c150
Source dataset
uspto-grants-1977_01
Patent number
US04001234

Reaction notes

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