Heptane → 2-(2-bromo-5-trityl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-7-chloroisoindolin-1-one

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Reaction Steps

2-bromo-5-trityl-pyrrolo[2,3-b]pyrazin-7-amine (4.82 g, 10.59 mmol) suspended in PhMe (72 mL) and AlMe3 in heptane (31 mL of 1.0 M, 31 mmol) added at RT under N2. After 30 minutes, a solution of 7-chloro-3H-isobenzofuran-1-one (3.570 g, 21.18 mmol) in DCM (72 mL) added with cooling on an ice bath. Reaction mixture stirred overnight, temperature rising to ambient. Reaction mixture re-cooled on an ice bath and water (˜30 mL) added slowly. After 5 minutes mixture diluted with DCM. Resulting mixture stirred vigorously for 30 mins then filtered through celite to remove bulk of Al salts. Layers separated. Aqueous extracted with DCM (×2). Combined organics dried and concentrated to a brown solid. This material dissolved in THF (200 mL) under N2 and Ph3P (4.165 g, 15.88 mmol) then DEAD (2.00 mL, 12.71 mmol) added. Reaction mixture stirred overnight at RT then concentrated. Residue partitioned between DCM and brine. Aqueous phase extracted with DCM and combined organics dried and concentrated. Resulting black residue taken up in DCM. Some product precipitates and is collected by filtration. Filtrate purified by chromatography (silica, 0-5% MeOH-DCM gradient elution). Product fractions concentrated to a brown solid and further purified by trituration with DCM/MeOH (˜1:1) to give a yellow solid. Combined product dried under vacuum at 60° C. to give the title compound as a yellow solid (2.39 g, 37% over two steps); 1H NMR (400 MHz, DMSO) δ 5.85 (2H, s), 7.76-7.84 (15H, m), 7.97 (1H, d), 8.12 (1H, t), 8.21 (1H, d), 8.54 (1H, s), 9.22 (1H, s) ppm; MS (ES+) 606.0.

Provenance & Evidence