Phosphorus oxychloride → 4-((4-Chloropyrimidin-2-yl)amino)benzonitrile
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]=1Participants
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).
Workup
- temperaturerefluxed under Argon for 20 minutes
- customthe solid was separated by filtration
- additionby adding a 20% NaOH solution
- customThe solid was again separated by filtration
- addition1000 ml CH2Cl2 was added
- temperatureThe mixture was heated until all solid
- dissolutionhad dissolved
- customthe aqueous layer was separated
- customthe organic layer was dried
- customDuring removal of the drying agent
- filtrationby filtration
- customa white solid formed in the filtrate
- temperatureFurther cooling of the filtrate in the freezer
- filtrationfollowed by filtration
Sources & evidence
- ORD record
- ord-a777135d01b447efb12613d4454ea042
- Source dataset
- uspto-grants-2013_09
- Patent number
- US08530655B2
Reaction notes
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