Ethyl Acetate → 2-(azidomethyl)-5-tosyl-5H-pyrrolo[2,3-b]pyrazine

Participants

Reaction Steps

To a solution of (5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanol (35.8 g, 118 mmol) in DCM (600 mL) was added SOCl2 (21.5 mL, 295 mmol). After about 4 h at ambient temperature, additional SOCl2 (8.60 mL, 118 mmol) was added. After about 16 h, the reaction was concentrated under reduced pressure and washed with saturated aqueous NaHCO3 (1000 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was dissolved in DCM (600 mL) and re-subjected to SOCl2 (21.51 mL, 295 mmol). After about 16 h at ambient temperature, the reaction was concentrated under reduced pressure followed by the addition of DCM (500 mL) and saturated aqueous NaHCO3 (500 mL). The layers were separated and the organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. To the resulting residue was added DMF (500 mL) followed by NaN3 (38.3 g, 589 mmol). After about 16 h, at ambient temperature EtOAc (500 mL) was added and the organic solution was washed with water:brine (1:1, 2000 mL). The layers were separated and the aqueous layer was further extracted with EtOAc (500 mL). The combined organic layers were washed with brine (3×1000 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to provide 2-(azidomethyl)-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (32.65 g, 82% yield) as a tan solid: LC/MS (Table 2, Method a) Rt=2.31 min; MS m/z: 329 (M+H)+.

Provenance & Evidence