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

Participants

Reaction Conditions

Reaction Steps

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 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)+.

Provenance & Evidence