Hydrochloric Acid → 3-{1'-[(1-cyclopropyl-4-methoxy-1H-indol-6-yl)carbonyl]-4-oxospiro[chroman-2,4'-piperidin]-6-yl}benzoic acid

Participants

Reaction Conditions

Reaction Steps

N,N′-carbonyldiimidazole (130 mg) and triethylamine (0.446 mL) were added to a solution of 1-cyclopropyl-4-methoxy-1H-indole-6-carboxylic acid (185 mg) in DMF (4 mL), and stirred at 70° C. for 7 hours. To the reaction mixture was added 3-(4-oxo-spiro[chroman-2,4′-piperidin]-6-yl)benzoic acid hydrochloride (374 mg), which was further stirred at that temperature for 16 hours. 1 N hydrochloric acid and water were added to the reaction mixture, and the formed solid was collected by filtration. The resulting solid was recrystallized from methanol, and purified through silica gel column chromatography (chloroform/methanol) to obtain 3-{1′-[(1-cyclopropyl-4-methoxy-1H-indol-6-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}benzoic acid. This was suspended in water (5 mL), and aqueous 1 N sodium hydroxide solution (0.762 mL) was added thereto and stirred at room temperature for 30 minutes. The solution was purified through ODS reversed-phase column chromatography (water/methanol) to obtain the intended compound. 1H-NMR (400 MHz, DMSO-d6) δ: 8.11-8.09 (1H, m), 7.96-7.93 (1H, m), 7.90 (1H, dd, J=8.5, 2.4 Hz), 7.83-7.79 (1H, m), 7.56-7.50 (1H, m), 7.32 (1H, dd, J=7.6, 7.6 Hz), 7.29 (1H, d, J=3.2 Hz), 7.23 (1H, s), 7.20 (1H, d, J=8.5 Hz), 6.59 (1H, s), 6.41-6.39 (1H, m), 4.45-4.11 (1H, br m), 3.86 (3H, s), 3.86-3.55 (1H, br m), 3.52-3.22 (3H, m), 2.93 (2H, s), 2.17-1.64 (4H, br m), 1.11-1.00 (2H, m), 0.96-0.88 (2H, m); MS [M+Na]+=573.

Provenance & Evidence