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

HRID 1628104Notes

Reaction equation

HRID 1628104 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.BrC1C(N)=NC=C(Br)N=1.C([Si](C)(C)C)#C.[H-].[Na+].[S:32](Cl)([C:35]1[CH:41]=[CH:40][C:38]([CH3:39])=[CH:37][CH:36]=1)(=[O:34])=[O:33]>CN(C=O)C>[Br:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:10][N:8]([S:32]([C:35]3[CH:41]=[CH:40][C:38]([CH3:39])=[CH:37][CH:36]=3)(=[O:34])=[O:33])[C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 5

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 66111TrimethylsilylacetyleneHCID 6200042-Amino-3,5-dibromopyrazineHCID 533931895-Bromo-3-[(trimethylsilyl)ethynyl]pyrazin-2-amine

Product 1

HCID 529876432-Bromo-5-((4-methylphenyl)sulfonyl)-5H-pyrrolo(2,3-b)pyrazineYield 52%

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, prepared using A from 3,5-dibromopyrazin-2-amine with ethynyltrimethylsilane) in DMF (60 mL) at about 0° C. was added 60 wt % NaH (0.577 g, 14.4 mmol) in three portions. After about 15 min, TsCl (2.75 g, 14.4 mmol) was added and the mixture was allowed to warm slowly to rt. After about 16 h, the mixture was poured into 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 to give 2-bromo-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (2.16 g, 52%): LC/MS (Table 2, Method c) Rt=1.58 min; MS m/z: 352 (M+H)+.

Workup

  1. customat about 0° C.
  2. waitAfter about 16 h
  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

Sources & evidence

ORD record
ord-248bfa9786e5410ca25303179907d889
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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