4-Toluenesulfonyl chloride → 2-Bromo-5-((4-methylphenyl)sulfonyl)-5H-pyrrolo(2,3-b)pyrazine

HRID 1854314Notes

Reaction equation

HRID 1854314 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([C:9]#[C:10][Si](C)(C)C)[C:5]([NH2:8])=[N:6][CH:7]=1.[H-].[Na+].[C:17]1([CH3:27])[CH:22]=[CH:21][C:20]([S:23](Cl)(=[O:25])=[O:24])=[CH:19][CH:18]=1>CN(C=O)C>[Br:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:10][N:8]([S:23]([C:20]3[CH:21]=[CH:22][C:17]([CH3:27])=[CH:18][CH:19]=3)(=[O:25])=[O:24])[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 533931895-Bromo-3-[(trimethylsilyl)ethynyl]pyrazin-2-amine

Product 1

HCID 529876432-Bromo-5-((4-methylphenyl)sulfonyl)-5H-pyrrolo(2,3-b)pyrazineYield 55.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (3.00 g, 11.1 mmol) in DMF (60 mL) at about 0° C. was added NaH (60% dispersion in mineral oil, 0.577 g, 14.4 mmol) in three portions. After about 15 min, p-toluenesulfonyl chloride (2.75 g, 14.4 mmol) was added and the reaction was allowed to warm slowly to ambient temperature. After about 16 h, the reaction mixture was poured onto ice-cold water (120 mL) and the precipitate was collected by vacuum filtration. The crude solid was dissolved in DCM (15 mL) and purified by silica gel chromatography eluting with DCM. The product-containing fractions were concentrated under reduced pressure to give 2-bromo-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (2.16 g, 52%): LC/MS (Table 2, Method d) Rt=1.58 min; MS m/z: 352/354 (M+H)+.

Workup

  1. waitAfter about 16 h
  2. additionthe reaction mixture was poured onto ice-cold water (120 mL)
  3. filtrationthe precipitate was collected by vacuum filtration
  4. dissolutionThe crude solid was dissolved in DCM (15 mL)
  5. custompurified by silica gel chromatography
  6. washeluting with DCM
  7. concentrationThe product-containing fractions were concentrated under reduced pressure

Sources & evidence

ORD record
ord-67632611cb044297844ab1814e33b5b2
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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