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

HRID 716029Notes

Reaction equation

HRID 716029 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]([CH2:23][CH2:24][O:25][CH2:26]Cl)([CH3:22])[CH3:21]>CN(C=O)C.O>[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]([CH2:26][O:25][CH2:24][CH2:23][Si:20]([CH3:22])([CH3:21])[CH3:19])[C:7]2=[N:8][CH:9]=1

Participants

6

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-oneYield 91.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a 100 ml three necked round bottom flask, sodium hydride (60% in paraffin) (0.744 g, 0.0186 mole) was taken in DMF (10.0 ml). To this, 1-(2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-yl)-2,2-dimethyl propan-1-one (5.0 g, 0.1773 mole) in DMF (15 ml) was slowly added at 0° C. over 15 min under nitrogen atmosphere. After addition was complete, the reaction mixture was stirred for 10 min at same temperature followed by dropwise addition of SEM chloride (3.1 g, 0.0186 mole) at 0° C. After completion of the addition, the reaction mixture was warmed up to RT and stirred for 30 min. After completion of the reaction, the reaction mixture was poured in water and the aq. Layer was extracted with ethyl acetate. Organic layers were combined, washed with brine solution, dried over Na2SO4, filtered and concentrated to afford crude product which was subjected for the column purification. The crude compound was purified using column purification by eluting the compound with 10-15% ethyl acetate in hexanes to yield 7.0 g of 1-(2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-yl)-2,2-dimethylpropane-1-one.

Workup

  1. additionAfter addition
  2. additionAfter completion of the addition
  3. stirringstirred for 30 min
  4. customAfter completion of the reaction
  5. extractionthe aq. Layer was extracted with ethyl acetate
  6. washwashed with brine solution
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford crude product which
  11. customwas subjected for the column purification
  12. customThe crude compound was purified
  13. customcolumn purification
  14. washby eluting the compound with 10-15% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-a4fa14194ce34c10aef01c1bda53941b
Source dataset
uspto-grants-2015_11
Patent number
US09187487B2

Reaction notes

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