Phosphorus oxychloride → 4-Chloro-1-(3-chloropyridin-2-YL)-1H-pyrazolo[3,4-D]pyrimidine
Reaction equation
P(Cl)(Cl)([Cl:3])=O.[Cl:6][C:7]1[C:8]([N:13]2[C:17]3=[N:18][CH:19]=[N:20][C:21](O)=[C:16]3[CH:15]=[N:14]2)=[N:9][CH:10]=[CH:11][CH:12]=1>>[Cl:3][C:21]1[N:20]=[CH:19][N:18]=[C:17]2[N:13]([C:8]3[C:7]([Cl:6])=[CH:12][CH:11]=[CH:10][N:9]=3)[N:14]=[CH:15][C:16]=12Participants
Conditions
- Temperature
- 100 °C
Procedure
Phosphoryl trichloride (235 mL, 2455.17 mmol) was added to 1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-ol B15b (30.4 g, 122.76 mmol). The resulting solution was stirred at 100° C. for 4 hours. The mixture was concentrated in vacuo and to the residue was added an ice/water mixture. The resulting mixture was stirred for 1 hour during which time a solid precipitated. The solid was collected by filtration and washed with water (3×75 mL). The crude product was dissolved in EtOAc (500 mL) and dried over MgSO4, filtered and evaporated to afford 4-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (28.7 g). 1H NMR (400 MHz, DMSO-d6) δ 7.78 (1H, dd), 8.37 (1H, dd), 8.69 (1H, dd), 8.83 (1H, s), 8.92 (1H, s), m/z (ESI+) (M+H)+=266; HPLC tR=1.72 min.
Workup
- concentrationThe mixture was concentrated in vacuo and to the residue
- additionwas added an ice/water mixture
- stirringThe resulting mixture was stirred for 1 hour during which time a solid
- customprecipitated
- filtrationThe solid was collected by filtration
- washwashed with water (3×75 mL)
- dissolutionThe crude product was dissolved in EtOAc (500 mL)
- dry with materialdried over MgSO4
- filtrationfiltered
- customevaporated
Sources & evidence
- ORD record
- ord-391858ab5c4349cd9388526f427a452b
- Source dataset
- uspto-grants-2012_03
- Patent number
- US08143263B2
Reaction notes
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