Maleimide → 3-(4-methoxybenzyl)pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dione

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Reaction Conditions

Reaction Steps

1-(4-methoxybenzyl)-1H-pyrazol-5-amine hydrochloride (2.0 g, 8.35 mmol) was free-based with 10% aqueous potassium carbonate (100 ml) and extracted with diethyl ether (100 ml). The organic layer was concentrated under reduced pressure to afford a yellow solid. N,N-dimethylformamide dimethylacetal (15 ml) was added and the mixture heated to 120° C. for 2.5 hours. The mixture was concentrated under reduced pressure which was then treated with maleimide (1.62 g, 16.7 mmol) and acetic acid (10 ml) and heated to 50° C. for 2 days. The mixture was poured into cold water (250 ml) and extracted with ethyl acetate (3×100 ml). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to afford 3-(4-methoxybenzyl)pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dione as a pale yellow solid (593 mg, 23%). M.p.=196-197° C.; 400 MHz 1H NMR (DMSO-d6) δ: 11.55 (s, 1H), 9.02 (s, 1H), 8.50 (s, 1H), 7.24 (d, J=8.8 Hz, 2H), 6.85 (d, J=8.8 Hz, 2H), 5.70 (s, 2H), 3.68 (s, 3H); LCMS: 309 [M+H]. 1-(4-methoxybenzyl)-1H-pyrazol-5-amine hydrochloride was made according to the procedure described in Bioorganic and Medicinal Chemistry Letters, vol. 13, pp. 1133-6 (2003).

Provenance & Evidence