Sodium hydride → tert-butyl 2-amino-2-oxoethyl(5-tosyl-5H-pyrrolo[3,2-b]pyrazin-2-yl)carbamate

HRID 1969609Notes

Reaction equation

HRID 1969609 reaction equation
[S:1]([N:11]1[C:19]2[C:14](=[N:15][C:16]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:17][N:18]=2)[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[H-].[Na+].Br[CH2:31][C:32]([NH2:34])=[O:33]>CN(C=O)C>[NH2:34][C:32](=[O:33])[CH2:31][N:20]([C:16]1[N:15]=[C:14]2[CH:13]=[CH:12][N:11]([S:1]([C:4]3[CH:5]=[CH:6][C:7]([CH3:8])=[CH:9][CH:10]=3)(=[O:2])=[O:3])[C:19]2=[N:18][CH:17]=1)[C:21](=[O:27])[O:22][C:23]([CH3:24])([CH3:26])[CH3:25]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 696322-BromoacetamideHCID 580097831,1-Dimethylethyl N-(5-((4-methylphenyl)sulfonyl)-5H-pyrrolo(2,3-b)pyrazin-2-yl)carbamate

Product 1

HCID 58557503tert-butyl 2-amino-2-oxoethyl(5-tosyl-5H-pyrrolo[3,2-b]pyrazin-2-yl)carbamateYield 85.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl 5-tosyl-5H-pyrrolo[3,2-b]pyrazin-2-ylcarbamate (1.00 g, 2.57 mmol, Example #3 Step E) and DMF (13 mL) under nitrogen at about 0° C. was added NaH (60% dispersion in mineral oil, 0.113 g, 2.83 mmol) in one portion. After about 30 min, 2-bromoacetamide (0.391 g, 2.83 mmol) was added in one portion. After about 30 min, the ice bath was removed and the solution was stirred at ambient temperature for about 2 h. Saturated aqueous NH4Cl/water (1:1, 100 mL) was added. After stirring for about 10 min, the mixture was filtered using water to wash the filter cake. The aqueous phase was extracted with EtOAc (50 mL). The filter cake was dissolved in EtOAc and added to the organic layer. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was purified by silica gel chromatography eluting with a gradient of 20-100% EtOAc/heptane to give tert-butyl 2-amino-2-oxoethyl(5-tosyl-5H-pyrrolo[3,2-b]pyrazin-2-yl)carbamate (0.980 g, 82%): LC/MS (Table 1, Method n) Rt=0.70 min; MS m/z 446 (M+H)+.

Workup

  1. waitAfter about 30 min
  2. customthe ice bath was removed
  3. additionSaturated aqueous NH4Cl/water (1:1, 100 mL) was added
  4. stirringAfter stirring for about 10 min
  5. filtrationthe mixture was filtered
  6. washto wash the filter cake
  7. extractionThe aqueous phase was extracted with EtOAc (50 mL)
  8. dissolutionThe filter cake was dissolved in EtOAc
  9. additionadded to the organic layer
  10. dry with materialThe organic layer was dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe material was purified by silica gel chromatography
  14. washeluting with a gradient of 20-100% EtOAc/heptane

Sources & evidence

ORD record
ord-79f1e650d080426eb686c32cd16d25ff
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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