Sodium hydride → 5-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine

HRID 1943869Notes

Reaction equation

HRID 1943869 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]2[C:12]([I:13])=[N:11][NH:10][C:7]2=[N:8][CH:9]=1.[CH3:14][Si:15]([CH3:22])([CH3:21])[CH2:16][CH2:17][O:18][CH2:19]Cl>CN(C=O)C>[Br:3][C:4]1[CH:5]=[C:6]2[C:12]([I:13])=[N:11][N:10]([CH2:19][O:18][CH2:17][CH2:16][Si:15]([CH3:22])([CH3:21])[CH3:14])[C:7]2=[N:8][CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178419453HCID 178419453, compound

Product 1

HCID 598361345-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridineYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH (1.31 g, 32.7 mmol, 60% suspension in mineral oil) was added portionwise to a cold (0° C.) solution of 5-bromo-3-iodo-1H-pyrazolo[3,4-b]pyridine (5.3 g, 16.4 mmol) in dry DMF (40 mL) The reaction mixture was stirred at 0° C. for 10 minutes before 2-(trimethylsilyl)ethoxymethyl chloride (4.91 mL, 27.8 mmol) was added dropwise via a syringe. The cold bath was removed, and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was placed in an ice bath, diluted with ethyl acetate (400 mL) and carefully quenched with water (50 mL). The aqueous layer was separated and extracted with ethyl acetate (3×50 mL). The combined organic layers were dried, filtered and concentrated. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (20:1) to give 5-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine (6.59 g, 89%) as a solid.

Workup

  1. additionwas added dropwise via a syringe
  2. customThe cold bath was removed
  3. customThe reaction mixture was placed in an ice bath
  4. additiondiluted with ethyl acetate (400 mL)
  5. customcarefully quenched with water (50 mL)
  6. customThe aqueous layer was separated
  7. extractionextracted with ethyl acetate (3×50 mL)
  8. customThe combined organic layers were dried
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified by column chromatography
  12. washeluting with hexanes/ethyl acetate (20:1)

Sources & evidence

ORD record
ord-b87a72de74b34710a01cd94ff86810da
Source dataset
uspto-grants-2013_03
Patent number
US08394795B2

Reaction notes

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