Sodium hydride → 1-(2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-yl)-2,2-dimethylpropane-1-one

HRID 600379Notes

Reaction equation

HRID 600379 reaction equation
[H-].[Na+].[Br:3][C:4]1[N:5]=[C:6]2[C:12]([C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:11][NH:10][C:7]2=[N:8][CH:9]=1.[CH3:19][Si:20]([CH3:27])([CH3:26])[CH2:21][CH2:22][O:23][CH2:24]Cl>CN(C=O)C>[Br:3][C:4]1[N:5]=[C:6]2[C:12]([C:13](=[O:18])[C:14]([CH3:15])([CH3:17])[CH3:16])=[CH:11][N:10]([CH2:24][O:23][CH2:22][CH2:21][Si:20]([CH3:27])([CH3:26])[CH3:19])[C:7]2=[N:8][CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 578292181-(2-Bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethylpropan-1-one

Product 1

HCID 578292211-(2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-yl)-2,2-dimethylpropane-1-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
2.5 °C

Procedure

Sodium hydride (60% in mineral oil, 0.019 g, 0.48 mmol) was added to a stirring solution of 1-(2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one (0.094 g, 0.33 mmol) in 1.5 mL of N,N′-dimethylformamide at 0-5° C. The bubbling yellow mixture was stirred at 0-5° C. for 15 min., then 2-(trimethylsilyl)ethoxymethyl chloride (0.075 mL, 0.42 mmol) was added. The resulting cloudy yellow mixture was stirred at RT for 3 h, then partitioned between 10 mL of water and 10 mL of ethyl acetate. The organic layer was sequentially washed with two 10 mL portions of water and 10 mL of a sat. aq. NaCl solution, dried over MgSO4, filtered, and concentrated to an orange oil. Silica gel chromatography (10% EtOAc/hexanes) afforded 0.129 g (93%) of slightly impure 1-[2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one as a yellow oil that was used without further purification.

Workup

  1. stirringThe resulting cloudy yellow mixture was stirred at RT for 3 h
  2. custompartitioned between 10 mL of water and 10 mL of ethyl acetate
  3. washThe organic layer was sequentially washed with two 10 mL portions of water and 10 mL of a sat. aq. NaCl solution
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to an orange oil

Sources & evidence

ORD record
ord-97d8f962459e46b29fa87f6fedb60bd4
Source dataset
uspto-grants-2011_03
Patent number
US07902197B2

Reaction notes

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