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

HRID 1854428Notes

Reaction equation

HRID 1854428 reaction equation
[Br:1][C:2]1[N:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[H-].[Na+].[C:13]1([CH3:23])[CH:18]=[CH:17][C:16]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:14]=1.[OH-].[Na+]>CN(C=O)C>[Br:1][C:2]1[N:3]=[C:4]2[CH:10]=[CH:9][N:8]([S:19]([C:16]3[CH:17]=[CH:18][C:13]([CH3:23])=[CH:14][CH:15]=3)(=[O:21])=[O:20])[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 250673082-bromo-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 529876432-Bromo-5-((4-methylphenyl)sulfonyl)-5H-pyrrolo(2,3-b)pyrazineYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
2.5 °C

Procedure

A solution of 2-bromo-5H-pyrrolo[2,3-b]pyrazine (78.0 g, 394 mmol, Ark Pharm) in anhydrous DMF (272 mL) was added drop-wise over about 60 min to a stirred suspension of NaH (60% dispersion in mineral oil, 12.8 g, 532 mmol) in anhydrous DMF (543 mL) at about 0-5° C. The brown reaction solution was stirred for about 30 min at about 0-5° C. then a solution of p-toluenesulfonyl chloride (94.0 g, 492 mmol) in anhydrous DMF (272 mL) was added drop-wise over about 60 min at about 0-5° C. The reaction mixture was stirred at about 0-5° C. for about 1 h then allowed to warm to ambient temperature and stirred for about 18 h. The reaction mixture was poured slowly into ice water (6 L), followed by the addition of aqueous NaOH (2.5 M, 50.0 mL, 125 mmol). The precipitate was collected by filtration and stirred with cold water (3×200 mL). The solid was collected by filtration and dried to constant weight in a vacuum oven at about 55° C. to yield 2-bromo-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (134.6 g, 97%) as a pale beige solid: LC/MS (Table 2, Method d) Rt=1.58 min; MS m/z: 352/354 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred at about 0-5° C. for about 1 h
  2. temperatureto warm to ambient temperature
  3. stirringstirred for about 18 h
  4. filtrationThe precipitate was collected by filtration
  5. stirringstirred with cold water (3×200 mL)
  6. filtrationThe solid was collected by filtration
  7. customdried to constant weight in a vacuum oven at about 55° C.

Sources & evidence

ORD record
ord-4cd46e5122f84ca78202125fdf12a11d
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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