Phosphorus oxychloride → 6-chloro-1-(3,3,4,4,4-pentafluorobutyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile
Reaction equation
[C:1]([C:3]1[C:11]2[C:6](=[N+:7]([O-])[CH:8]=[CH:9][CH:10]=2)[N:5]([CH2:13][CH2:14][C:15]([F:21])([F:20])[C:16]([F:19])([F:18])[F:17])[N:4]=1)#[N:2].O=P(Cl)(Cl)[Cl:24]>>[Cl:24][C:8]1[N:7]=[C:6]2[N:5]([CH2:13][CH2:14][C:15]([F:21])([F:20])[C:16]([F:19])([F:18])[F:17])[N:4]=[C:3]([C:1]#[N:2])[C:11]2=[CH:10][CH:9]=1Participants
Conditions
- Temperature
- 75 °C
Procedure
To the intermediate from Step A above (225 mg, 0.735 mmol) was added POCl3 (2.8 g, 18.3 mmol) and the mixture was stirred at 75° C. for 9 hours. The reaction mixture was then concentrated in vacuo to remove POCl3. To the residue was added hexane/ethyl acetate (2/1, 50 mL) and the pH adjusted to 7.5˜8.0 with aqueous K2CO3 at 0° C. The water layer was extracted with the hexane/ethyl acetate (2/1, 2×20 mL). The combined organic layer was dried over Na2SO4 and evaporated under reduced pressure. The residue was purified by silica gel column chromatography using hexane/ethyl acetate eluent to give the product as a white solid. 1H NMR (500 MHz, CDCl3): δ 2.86 (m, 2H); 4.90 (t, J=8.4 Hz, 2H); 7.42 (d, J=8.4 Hz, 1H); 8.17 (d, J=8.4 Hz, 1H), m/z=325.04 (M+H).
Workup
- concentrationThe reaction mixture was then concentrated in vacuo
- customto remove POCl3
- additionTo the residue was added hexane/ethyl acetate (2/1, 50 mL)
- customadjusted to 7.5˜8.0 with aqueous K2CO3 at 0° C
- extractionThe water layer was extracted with the hexane/ethyl acetate (2/1, 2×20 mL)
- dry with materialThe combined organic layer was dried over Na2SO4
- customevaporated under reduced pressure
- customThe residue was purified by silica gel column chromatography
Sources & evidence
- ORD record
- ord-cf2abfcf4f2c44fa9427e5094c344faf
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09365574B2
Reaction notes
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