Acetic Acid → HCID 59408993, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(5-bromo-1H-indol-3-yl)-acetamide (500 mg, 1.98 mmol) and oxo-(1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-8-yl)-acetic acid methyl ester (404 mg, 1.65 mmol) in anhydrous tetrahydrofuran at 0° C. was added a solution of potassium tert-butoxide (4.95 ml, 4.95 mmol; 1M solution in tetrahydrofuran) dropwise over 5 minutes. The reaction was stirred for a further 30 minutes then cooled to 0° C. and quenched with water (50 ml) and acidified to pH6 with aqueous 2M hydrochloric acid. The mixture was extracted with dichloromethane (3×50 ml) and the combined organic extracts were dried over anhydrous sodium sulfate and evaporated to dryness. The residue was dissolved in N,N-dimethylformamide (4 ml) and treated with piperidine (99 μl, 1.00 mmol) and acetic acid (57 μl, 1.00 mmol). The mixture was heated to 150° C. for 5 minutes under microwave conditions then partitioned between ethyl acetate (50 ml) and water (30 ml). The aqueous layer was removed and the organic layer was washed with water (2×30 ml). The organic layer was dried over anhydrous sodium sulfate and evaporated to dryness. The residue was purified by flash column chromatography (SiO2, 1% methanol to 10% methanol in dichloromethane) to provide 3-(5-bromo-1H-indol-3-yl)-4-(1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-8-yl)-pyrrole-2,5-dione as a red solid (340 mg). 400 MHz 1H NMR (CDCl3) δ: 8.71 (s, 1H), 7.96 (d, J=2.4 Hz, 1H), 7.48 (s, 1H), 7.27 (m, 2H), 7.08 (s, 1H), 6.94 (s, 1H), 6.56 (s, 1H), 3.36 (t, J=8.0 Hz, 2H), 3.07 (m, 2H), 3.83 (t, J=8.0 Hz, 2H), 2.47 (t, J=6.8 Hz, 2H), 2.04 (m, 2H); LCMS: 448 and 450 [M+H].

Provenance & Evidence