3-(4-Methoxybenzyl)-7-phenethylpyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3h,7h)-dione → 7-phenethylpyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dione

Participants

Reaction Conditions

Reaction Steps

To an ice cooled solution of 3-(4-methoxybenzyl)pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dione (2.5 g, 8.1 mmol) in anhydrous N,N-dimethylformamide (25 ml), sodium hydride (60% emulsion in paraffin oil, 500 mg, 12 mmol) was added. The reaction mixture was warmed to room temperature and stirred for 10 minutes. The reaction mixture was again cooled to 0° C. and (2-bromoethyl)benzene (1.5 ml, 8.9 mmol) was added. The solution was then heated to 90° C. for 2 hours. The reaction was monitored by TLC and LCMS, and on completion of reaction, it was cooled to room temperature and ice cooled water (75 ml) was added. The reaction mixture was then extracted with ethyl acetate (3×150 ml). The combined ethyl acetate layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a residue which was purified by column chromatography on silica gel using a gradient of 0-20% ethyl acetate in hexanes to afford 3-(4-methoxybenzyl)-7-phenethylpyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dione (2 g, 60%) as a solid. 1HNMR (400 MHz, DMSO-d6) δ: 9.05 (s, 1H), 8.65 (s, 1H), 7.15-7.3 (m, 7H), 6.85 (d, 2H), 5.77 (s, 2H), 3.85 (t, 2H), 3.70 (s, 3H), 2.95 (t, 2H); LCMS: [M+H] 413. Trifluoroacetic acid (20 ml) was added to 3-(4-methoxybenzyl)-7-phenethylpyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dione (1 g, 2.1 mmol) at 0° C., and then stirred at 100° C. for 5 hours. The reaction was monitored by TLC, and on completion of the reaction, trifluoroacetic acid was evaporated under reduced pressure and the residue was basified using aqueous ammonia to form a solid precipitate. The solid was filtered over a sintered funnel. The solid was washed with hexane and dried under reduced pressure to afford 7-phenethylpyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dione (500 mg, 80%). The compound was used next without further purification. 1HNMR (400 MHz, DMSO-d6) δ: 14.50 (s, 1H), 9.00 (s, 1H), 8.50 (s, 1H), 7.05-7.15 (m, 5H), 3.95 (t, 2H), 2.95 (t, 2H); LCMS: [M+H] 293.

Provenance & Evidence