Phosphorus oxychloride → 4-Chloro-6-(3,4-dimethoxyphenyl)pyrazolo[1,5-a]pyrazine
Reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[NH:12][C:13](=O)[C:14]3[N:15]([N:17]=[CH:18][CH:19]=3)[CH:16]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].P(Cl)(Cl)([Cl:23])=O>O>[Cl:23][C:13]1[C:14]2[N:15]([N:17]=[CH:18][CH:19]=2)[CH:16]=[C:11]([C:5]2[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)[N:12]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 95 °C
Procedure
6-(3,4-dimethoxyphenyl)pyrazolo[1,5-a]pyrazin-4(5H)-one 5.02 (74 mg, 0.27 mmol) was taken up in phosphorous oxychloride (1.4 mL, 15 mmol) and mixture was heated to 95° C. for two hours. After cooling to room temperature, mixture was carefully added via pipet to vigorously stirring water (15 mL) with internal temperature monitoring, at a rate to keep the internal temperature below 45° C. Reaction flask was washed with 15 mL of ethyl acetate and added to aqueous mixture to ensure complete transfer. Layers were separated and aqueous was extracted with ethyl acetate. Combined organic layers were washed with 1:1 brine/saturated NaHCO3 (aq), dried (Na2SO4), filtered, and concentrated under reduced pressure to yield 4-chloro-6-(3,4-dimethoxyphenyl)pyrazolo[1,5-a]pyrazine 5.03. LCMS-ESI+ (m/z): [M+H]+ calcd for C14H13ClN3O2: 290.06; found: 290.10.
Workup
- temperatureAfter cooling to room temperature
- customthe internal temperature below 45° C
- customReaction flask
- washwas washed with 15 mL of ethyl acetate
- additionadded to aqueous mixture
- customLayers were separated
- extractionaqueous was extracted with ethyl acetate
- washCombined organic layers were washed with 1:1 brine/saturated NaHCO3 (aq)
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-456b322ba19444de80168050bf06ae52
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09376441B2
Reaction notes
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