反应详情

温度

80 °C

N-Carbamoylmethyl-4-oxospiro[chroman-2,4′-piperidine]-6-carboxamide hydrochloride (389 mg), 1-cyclopropyl-4-ethoxy-1H-indole-6-carboxylic acid (245 mg), WSC hydrochloride (230 mg), HOBT (183 mg) and triethylamine (0.209 mL) were suspended in DMF (8 mL), and the mixture was stirred at 80° C. for 1.5 hours. The reaction mixture was allowed to cool to room temperature, diluted with ethyl acetate, and washed successively with water, 1 N hydrochloric acid, aqueous saturated sodium bicarbonate and saturated saline water. The organic layer was dried over sodium sulfate, filtered, concentrated, and purified through silica gel column chromatography (chloroform/methanol) to afford the title compound as a colorless amorphous substance. 1H-NMR (400 MHz, DMSO-d6) δ: 8.78-8.71 (1H, m), 8.32-8.30 (1H, m), 8.08 (1H, dd, J=8.7, 2.3 Hz), 7.34 (1H, s), 7.28 (1H, d, J=3.4 Hz), 7.22-7.16 (2H, m), 6.99 (1H, s), 6.56 (1H, s), 6.38 (1H, d, J=3.4 Hz), 4.27-4.15 (1H, br m), 4.15 (2H, q, J=7.0 Hz), 3.77 (2H, d, J=5.9 Hz), 3.46-3.25 (3H, br m), 3.45-3.39 (1H, m), 2.95 (2H, s), 2.09-1.75 (4H, br m), 1.38 (3H, t, J=7.0 Hz), 1.08-1.01 (2H, m), 0.95-0.90 (2H, m); MS [M+H]+=545.

1. temperatureto cool to room temperature
2. washwashed successively with water, 1 N hydrochloric acid, aqueous saturated sodium bicarbonate and saturated saline water
3. dry with materialThe organic layer was dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. custompurified through silica gel column chromatography (chloroform/methanol)