反应详情

Starting materials: methyl 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxylate and 2-aminoethanesulfonamide hydrochloride, but the reaction mixture was heated at 80° C. for 22 h. After the first 2 h, an additional 6 eqv. of trimethylaluminium was added to the reaction mixture. The mixture was cooled, diluted with a saturated sodium hydrogen carbonate solution (10 mL) and concentrated in vacuo. The residue was suspended in methanol/dichloromethane, (1:1), silica gel (˜2 g) was added and the mixture was re-concentrated in vacuo, resulting in a fine yellow powder that was purified on a silica gel column using dichloromethane/methanol/aqueous NH3, (first 100:10:1, then 70:10:1), as the eluent to afford the title compound as a base in 40% yield: 1H NMR (DMSO-d6, 300 MHz) δ 14.5 (br s, 1H), 11.29 (br s, 1H), 10.69 (s, 1H), 8.61 (br s, 1H), 8.22 (s, 1H), 8.04 (d, J=9.0 Hz, 1H), 7.98 (s, 1H), 7.82 (d, J=9.0 Hz, 1H), 7.51 (d, J=8.2 Hz, 1H), 6.96-6.90 (m, 3H), 4.25 (s, 2H), 3.98-3.64 (m, 14H), 3.36-3.22 (m, 4H), 3.12-3.04 (m, 2H); MS (ES) m/z 460 (M++1). The base was converted to the hydrochloride

1. temperatureThe mixture was cooled
2. concentrationconcentrated in vacuo
3. additionwas added
4. concentrationthe mixture was re-concentrated in vacuo
5. customresulting in a fine yellow powder that
6. customwas purified on a silica gel column