Phosphorus oxychloride → HCID 86672829, compound
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3=[CH:13][N:14]=[N:15][C:16](O)=[C:11]3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:20].C(=O)(O)[O-].[Na+]>CCOC(C)=O>[Cl:20][C:16]1[N:15]=[N:14][CH:13]=[C:12]2[N:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[N:9]=[CH:10][C:11]=12Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 100 °C
Procedure
A mixture of 1-(4-fluorophenyl)-1H-pyrazolo[3,4-d]pyridazin-4-ol (1.30 g, 5.65 mmol), and POCl3 (25 mL) is warmed at 100° C. After 4 hours, the reaction mixture is cooled to room temperature and added dropwise to ice cold water, followed by periodic addition of crushed ice to control the exotherm. To the aqueous solution is added EtOAc and the mixture is neutralized with sodium bicarbonate. The organic layer is separated and the aqueous layer is extracted with EtOAc (3×50 mL). The combined organic layers are washed with saturated aqueous sodium bicarbonate (2×30 mL) and brine (2×30 mL), dried over magnesium sulfate, filtered and concentrated to afford 4-chloro-1-(4-fluorophenyl)-1H-pyrazolo[3,4-d]pyridazine, which is used without purification.
Workup
- temperaturethe reaction mixture is cooled to room temperature
- additionadded dropwise to ice cold water
- additionfollowed by periodic addition of crushed ice
- customThe organic layer is separated
- extractionthe aqueous layer is extracted with EtOAc (3×50 mL)
- washThe combined organic layers are washed with saturated aqueous sodium bicarbonate (2×30 mL) and brine (2×30 mL)
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-276f75d76b4146568a0393d9de42ac62
- Source dataset
- uspto-grants-2015_01
- Patent number
- US08927550B2
Reaction notes
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