Heptane → 5-Bromo-2-[2-(4-isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-yl]isoindolin-1-one

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Reaction Steps

2-(4-isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-amine (332 mg, 0.5942 mmol) dissolved in PhMe (5 mL) and AlMe3 in heptane (1.783 mL of 1.0 M, 1.783 mmol) added at RT under N2. After 30 minutes, a solution of 5-bromo-3H-isobenzofuran-1-one (253 mg, 1.188 mmol) in DCM (5 mL) added with cooling in an ice bath. RM stirred overnight, temperature rising to ambient. RM re-cooled in an ice bath and water (3 mL) added slowly. After 5 minutes, RM diluted with DCM. Resulting mixture filtered to remove bulk of Al salts. Brine added and the layers separated. Aqueous extracted with DCM (×2). Combined organics dried and concentrated to a brown foam (514 mg). This material dissolved in THF (6 mL) under N2 and PPh3 (233.8 mg, 0.8913 mmol) then DEAD (112 μL, 0.7130 mmol) added. Mixture stirred overnight at RT. RM concentrated and residue partitioned between DCM and brine. Aqueous phase extracted with DCM and combined extracts dried and concentrated. Residue treated with 1:1 DCM:MeOH and resulting pale yellow solid collected by filtration and dried under vacuum to give title compound (293 mg, 65%); 1H NMR (400 MHz, DMSO) δ 0.98 (6H, d), 3.28 (1H, sep), 5.40 (2H, s), 5.55 (2H, s), 7.05-7.18 (15H, m), 7.48 (1H, d), 7.55 (1H, dd), 7.74 (2H, d), 7.87 (1H, s), 8.28 (2H, d), 8.39 (1H, s), 8.67 (1H, s); MS (ES+) 754.0.

Provenance & Evidence