Phosphorus oxychloride → 4-((4-Chloropyrimidin-2-yl)amino)benzonitrile

HRID 1294433Notes

Reaction equation

HRID 1294433 reaction equation
O=[C:2]1[CH:7]=[CH:6][NH:5][C:4]([NH:8][C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=2)=[N:3]1.O=P(Cl)(Cl)[Cl:19]>>[Cl:19][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=2)[N:3]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178510039HCID 178510039, compound

Product 1

HCID 111955954-((4-Chloropyrimidin-2-yl)amino)benzonitrileYield 77.2%

Procedure

A mixture of 4-[(1,4-dihydro-4-oxo-2-pyrimidinyl)amino]benzonitrile, (0.12 mol) in POCl3 (90 ml) was stirred and refluxed under Argon for 20 minutes. The reaction mixture was slowly poured onto 750 ml ice/water, and the solid was separated by filtration. The solid was suspended in 500 ml water, and the pH of the suspension was adjusted to neutral by adding a 20% NaOH solution. The solid was again separated by filtration, suspended in 200 ml 2-propanone, and 1000 ml CH2Cl2 was added. The mixture was heated until all solid had dissolved. After cooling to room temperature, the aqueous layer was separated, and the organic layer was dried. During removal of the drying agent by filtration, a white solid formed in the filtrate. Further cooling of the filtrate in the freezer, followed by filtration, yielded 21.38 g (77.2%) of 4-[(4-chloro-2-pyrimidinyl)amino]benzonitrile (interm. 10). b) Intermediate (10) (0.005 mol), 1-bromo-2,5-pyrrolidinedione (0.006 mol) and trichloromethane (10 ml) were combined in a sealed tube and heated at 100° C. overnight. The reaction mixture was allowed to cool to room temperature. Silica gel (2 g) was added, and the solvent was evaporated. The residue was purified by flash column chromatography over silica gel (eluent: CH2Cl2/hexanes 9/1). The pure fractions were collected and the solvent was evaporated, yielding 1.31 g (84.5%) of 4-[(5-bromo-4-chloro-2-pyrimidinyl)amino]benzonitrile (interm. 11).

Workup

  1. temperaturerefluxed under Argon for 20 minutes
  2. customthe solid was separated by filtration
  3. additionby adding a 20% NaOH solution
  4. customThe solid was again separated by filtration
  5. addition1000 ml CH2Cl2 was added
  6. temperatureThe mixture was heated until all solid
  7. dissolutionhad dissolved
  8. customthe aqueous layer was separated
  9. customthe organic layer was dried
  10. customDuring removal of the drying agent
  11. filtrationby filtration
  12. customa white solid formed in the filtrate
  13. temperatureFurther cooling of the filtrate in the freezer
  14. filtrationfollowed by filtration

Sources & evidence

ORD record
ord-9836bb0f556b4456803575d78f761083
Source dataset
uspto-grants-2007_07
Patent number
US07241458B1

Reaction notes

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