反应详情

温度

35 °C

EDC (0.10 g, 0.52 mmol) was added to a solution of 3-(5,7,8,9-Tetrahydro-6-oxa-1,9-diaza-benzocyclohepten-3-yl)-acrylic acid hydrochloride (0.11 g, 0.43 mmol), HOBt (64 mg, 0.47 mmol), Methyl-(1-methyl-1H-indol-2-ylmethyl)-amine (128 mg, 0.47 mmol) and (i-Pr)2EtN (0.36 mL, 2.15 mmol) in DMF (6 mL). The mixture was allowed to stir overnight at 35° C. The mixture was cooled to 0° C. and diluted with H2O (15 mL) with rapid stirring. The resulting gummy precipitate was filtered, washed with H2O (30 mL) then with Et2O (20 mL). The solid was dissolved in dichloromethane (100 mL), washed with H2O (50 mL), brine (50 mL), dried over MgSO2, and treated with charcoal. The mixture was filtered and the filtrate was passed through a plug of silica gel. The silica gel was washed with ethyl acetate (50 mL) then with 5% methanol: dichloromethane (50 mL). The combined organic fractions were concentrated to give an oil. The resulting oil was triturated with ether:hexanes (20 mL) until the oil was converted to a beige solid. Yield: 40 mg (25%) as a mixture of amide rotamers; 1H NMR (400 MHz, DMSO-d6) δ 8.24 (br s, 1H), 7.92 and 7.85 (2×s, 1H), 7.50-7.39 (m, 3H), 7.18-6.92 (m, 3H), 6.78 (br s, 1H), 6.41 and 6.20 (2×s, 1H), 5.07 and 4.83 (2×s, 2H), 4.52 and 4.45 (2×s, 2H), 3.71-3.61 (m, 5H), 3.50-3.40 (m, 2H), 3.10 and 2.95 (2×s, 3H); ESI MS m/z 377 [C22H24N4O2+H]+

1. temperatureThe mixture was cooled to 0° C.
2. filtrationThe resulting gummy precipitate was filtered
3. washwashed with H2O (30 mL)
4. dissolutionThe solid was dissolved in dichloromethane (100 mL)
5. washwashed with H2O (50 mL), brine (50 mL)
6. dry with materialdried over MgSO2
7. additiontreated with charcoal
8. filtrationThe mixture was filtered
9. washThe silica gel was washed with ethyl acetate (50 mL)
10. concentrationThe combined organic fractions were concentrated
11. customto give an oil
12. customThe resulting oil was triturated with ether
13. additionYield: 40 mg (25%) as a mixture of amide rotamers