Phosphorus oxybromide → 3-bromo-7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine
Reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[N:10]1[CH2:15][CH2:14][CH2:13][C:12]2[C:16](=O)[N:17]([CH3:19])[NH:18][C:11]1=2.P(Br)(Br)([Br:23])=O>ClCCl>[Br:23][C:16]1[N:17]([CH3:19])[N:18]=[C:11]2[C:12]=1[CH2:13][CH2:14][CH2:15][N:10]2[C:3]1[C:4]([CH3:9])=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=1[Cl:1]Participants
Conditions
- Temperature
- 110 °C
Procedure
7-(2-Chloro-4,6-dimethylphenyl)-2-methyl-1,2,4,5,6,7-hexahydropyrazolo[3,4-b]pyridin-3-one (3.16 g) and phosphorus oxybromide (15.5 g) were combined and stirred in a 110° C. oil bath for 4 h. After the reaction mixture had cooled to room temperature, it was dissolved in dichloromethane and added to 200 mL of ice/water. This mixture was stirred vigorously for 30 min. The phases were then separated and the aqueous phase was washed with additional dichloromethane. The combined organic phases were washed with aqueous sodium bicarbonate, dried with magnesium sulfate, and concentrated on the rotary evaporator. The residue was chromatographed on silica gel eluting with an acetone/hexane gradient to provide 1.16 g of 3-bromo-7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine, mp 106-107° C.
Workup
- temperatureAfter the reaction mixture had cooled to room temperature
- stirringThis mixture was stirred vigorously for 30 min
- customThe phases were then separated
- washthe aqueous phase was washed with additional dichloromethane
- washThe combined organic phases were washed with aqueous sodium bicarbonate
- dry with materialdried with magnesium sulfate
- concentrationconcentrated on the rotary evaporator
- customThe residue was chromatographed on silica gel eluting with an acetone/hexane gradient
Sources & evidence
- ORD record
- ord-9fabad48be1c40cf830ef78faf92a189
- Source dataset
- uspto-grants-2007_09
- Patent number
- US07268146B2
Reaction notes
Loading…