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

HRID 1854435Notes

Reaction equation

HRID 1854435 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 (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 at ambient temperature. The reaction mixture was poured slowly into ice water (6 L), followed by the addition of aqueous 2.5 N NaOH (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 in air over about 3 days and finally 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 at ambient temperature
  4. filtrationThe precipitate was collected by filtration
  5. stirringstirred with cold water (3×200 mL)
  6. filtrationThe solid was collected by filtration
  7. customdried in air over about 3 days
  8. customfinally dried to constant weight in a vacuum oven at about 55° C.

Sources & evidence

ORD record
ord-c9a9157955184e80a41976772f3644de
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

Loading…