Sodium hydride → 1-benzyloxymethyl-4-chloro-1H-pyrazolo[3,4-b]pyridine

HRID 2070018Notes

Reaction equation

HRID 2070018 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][N:9]=[CH:10][C:3]=12.[H-].[Na+].[CH2:13]([O:20][CH2:21]Cl)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CN(C=O)C>[CH2:13]([O:20][CH2:21][N:8]1[C:4]2=[N:5][CH:6]=[CH:7][C:2]([Cl:1])=[C:3]2[CH:10]=[N:9]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 137983Benzyl chloromethyl etherHCID 3100454-Chloro-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 593985441-benzyloxymethyl-4-chloro-1H-pyrazolo[3,4-b]pyridineYield 58.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Chloro-1H-pyrazolo[3,4-b]pyridine (371 mg, 2.42 mmol) was dissolved in anhydrous DMF (1 mL), and sodium hydride (60%, 116 mg, 2.42 mmol) was added thereto. The resulting mixture was stirred under ice-cooling for 30 minutes, and then benzyloxymethyl chloride (0.48 mL, 3.39 mmol) was added thereto. The resulting mixture was stirred under ice-cooling for 1 hour and concentrated under reduced pressure. The residue was partitioned between ethyl acetate (80 mL) and saturated brine (20 mL). The aqueous layer was further extracted with ethyl acetate (70 mL). The combined organic layer was washed with saturated brine, dried, and concentrated. The residue was purified by silica-gel column chromatography (Fuji Silysia, BW300, 70 g, n-hexane:EtOAc=5:1) to give 1-benzyloxymethyl-4-chloro-1H-pyrazolo[3,4-b]pyridine as a light-yellow syrup (386 mg, yield: 58%).

Workup

  1. temperaturecooling for 30 minutes
  2. stirringThe resulting mixture was stirred under ice-
  3. temperaturecooling for 1 hour
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was partitioned between ethyl acetate (80 mL) and saturated brine (20 mL)
  6. extractionThe aqueous layer was further extracted with ethyl acetate (70 mL)
  7. washThe combined organic layer was washed with saturated brine
  8. customdried
  9. concentrationconcentrated
  10. customThe residue was purified by silica-gel column chromatography (Fuji Silysia, BW300, 70 g, n-hexane:EtOAc=5:1)

Sources & evidence

ORD record
ord-f274fe4a7493471883e4e9e99d91dac9
Source dataset
uspto-grants-2012_10
Patent number
US08299252B2

Reaction notes

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