Hydrochloric Acid → 5-(Aminomethyl)-6-chloro-N-(2,6-difluorophenyl)-2-(methylthio)-4-pyrimidinamine
Reaction equation
[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][C:11]2[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]=2[F:18])[N:5]=[C:4]([S:19][CH3:20])[N:3]=1.Cl.[OH-].[Na+]>>[NH2:9][CH2:8][C:7]1[C:6]([NH:10][C:11]2[C:12]([F:18])=[CH:13][CH:14]=[CH:15][C:16]=2[F:17])=[N:5][C:4]([S:19][CH3:20])=[N:3][C:2]=1[Cl:1]Participants
4
Procedure
To the solution of 4-chloro-6-[(2,6-difluorophenyl)amino]-2-(methylthio)-5-pyrimidinecarbonitrile (0.938 g) was added borane●THF complex (1.0 M, 15 mL). The reaction mixture was then heated at reflux for about 4 h until all the starting material disappeared. The solution was cooled to r.t., mixed with HCl solution (6 M, 5 mL), and stirred at room temperature for about 30 minutes. The solution was then mixed with NaOH solution (3 M) to pH 9.0-10.0. The organic phase was separated and the aqueous layer was extracted with EtOAc (3×30 mL). The combined organic layers were washed with brine (50 mL), collected, dried over Na2SO4 and concentrated to afford the title compound 0.97 g (quantative). LC-MS m/z 317 (M+H)+, 1.5 min (ret. time).
Workup
- temperatureThe reaction mixture was then heated
- temperatureat reflux for about 4 h until all the starting material
- customThe organic phase was separated
- extractionthe aqueous layer was extracted with EtOAc (3×30 mL)
- washThe combined organic layers were washed with brine (50 mL)
- customcollected
- dry with materialdried over Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-129902a13dc240719628951d6b18413c
- Source dataset
- uspto-grants-2009_01
- Patent number
- US07479558B2
Reaction notes
Loading…