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

HRID 646557Notes

Reaction equation

HRID 646557 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)benzonitrile

Procedure

In particular, 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 of 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 of 2-propanone, and 1000 ml of 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, i.e. the intermediate of formula (III-a).

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 of 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-48fa81403fc04a6493ddfbc555dfe899
Source dataset
uspto-grants-2010_04
Patent number
US07705148B2

Reaction notes

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