Sodium hydride → HCID 86667959, compound

HRID 1809699Notes

Reaction equation

HRID 1809699 reaction equation
[H-].[Na+].[Br:3][C:4]1[N:9]=[C:8]([C:10]2[C:18]3[C:13](=[N:14][C:15]([Cl:19])=[N:16][CH:17]=3)[NH:12][N:11]=2)[CH:7]=[CH:6][CH:5]=1.Cl[CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26]>CN(C=O)C>[Br:3][C:4]1[N:9]=[C:8]([C:10]2[C:18]3[C:13](=[N:14][C:15]([Cl:19])=[N:16][CH:17]=3)[N:12]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[N:11]=2)[CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178478327HCID 178478327, compound

Product 1

HCID 86667959HCID 86667959, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of NaH (1.3 mg, 37.6 mmol, 60%) in DMF (80 mL) was added slowly the solution of crude 3-(6-bromo-pyridin-2-yl)-6-chloro-1H-pyrazolo[3,4-d]pyrimidine (from Example 30 supra) (5.83 g, 18.8 mmol) in DMF (40 mL) at 5° C. The ice-bath was removed and the mixture was stirred for 20 minutes. Then (2-(chloromethoxy)ethyl)trimethylsilane (4.06 g, 24.4 mmol) was added. This solution was stirred for 12 hours at room temperature. The solvent was removed under reduced pressure. The residue was partitioned between saturated aqueous NH4Cl and dichloromethane (3×20 mL). The combined organics was dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 60 g, 200-300 mesh, eluting with ethyl acetate:petroleum ether, 1:10) to give 3-(6-bromo-pyridin-2-yl)-6-chloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidine as a white solid. (Yield 4.9 g, 84%).

Workup

  1. customThe ice-bath was removed
  2. stirringThis solution was stirred for 12 hours at room temperature
  3. customThe solvent was removed under reduced pressure
  4. customThe residue was partitioned between saturated aqueous NH4Cl and dichloromethane (3×20 mL)
  5. dry with materialThe combined organics was dried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography (silica gel, 60 g, 200-300 mesh, eluting with ethyl acetate:petroleum ether, 1:10)

Sources & evidence

ORD record
ord-276030ebeeba4333894e5f6517519972
Source dataset
uspto-grants-2013_01
Patent number
US08362023B2

Reaction notes

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