反应详情

10% Pd/C (0.035 g) was added to dimethyl 7-benzyloxy-4-(2-chloroethyl)-5-nitroindole-2,3-dicarboxylate (0.0718 g, 0.161 mmol) and chilled THF (5 mL) was added quickly to a flask. The mixture was placed under reduced pressure and purged three times with H2. The reaction was stirred under H2 at room temperature and atmospheric pressure until no starting material remained as indicated by TLC analysis. The solution was filtered through a Celite pad in a cinter funnel and washed with THF. The amine solution was concentrated under reduced pressure and the residue was co-evaporated twice with dry CH2Cl2 (3 mL each). To the amine were added EDCI (0.0617 g, 0.322 mmol) and 5,6,7-trimethoxyindole-2-carboxylic acid (0.0404 g, 0.161 mmol). The flask was sealed with a septum and flushed with N2. The mixture was then dissolved in dry DMF (6 mL) and stirred for three days under N2. The yellow solution was then diluted with ethyl acetate (150 mL), washed with water three times (100 mL each) and 5% NaHCO3 (50 mL). The organic layer was collected, dried with sodium sulfate, gravity filtered and concentrated under reduced pressure. The compound was purified on a chloroform silica gel column in which the solvent system was increased 0.5% MeOH/chloroform every 25 mL of solvent to give dimethyl 4-(2-chloroethyl)-7-hydroxy-5-(5,6,7-trimethoxyindole-2-carboxamido)indole-2,3-dicarboxylate as an off-white solid (17.8 mg, 0.032 mmol, 20% yield). Mp=166° C. (dec); TLC (2.5% MeOH/CHCl3) Rf320.23; 500 MHz 1H-NMR (CDCl3) 9.24 (s, 1H), 9.19 (s, 1H), 8.50 (s br, 1H), 7.25 (s, 1H), 7.10 (s br, 1H), 6.98 (s, 1H), 6.85 (s, 1H), 4.09 (s, 3H), 3.97 (s, 3H), 3.94 (s, 3H), 3.93 (s, 3H), 3.91 (s, 3H), 3.90 (t, 7.0, 2H), 3.31 (t, 7.0, 2H); IR (neat) 3282, 3090, 2954, 2918, 2851, 1730, 1713, 1685, 1610, 1535, 1510, 1476, 1415, 1376, 1307, 1262, 1204, 1096, 1050, 1030, 802. FAB-MS m/z (relative intensity) 560 (M+H+, 3), 559 (M+, 2). Accurate mass for C26H26N3O935Cl: calcd. 559.1358, obsd. 559.1350.

1. additionwas added quickly to a flask
2. custompurged three times with H2
3. filtrationThe solution was filtered through a Celite pad in a cinter funnel
4. washwashed with THF
5. concentrationThe amine solution was concentrated under reduced pressure
6. customThe flask was sealed with a septum
7. customflushed with N2
8. dissolutionThe mixture was then dissolved in dry DMF (6 mL)
9. stirringstirred for three days under N2
10. additionThe yellow solution was then diluted with ethyl acetate (150 mL)
11. washwashed with water three times (100 mL each) and 5% NaHCO3 (50 mL)
12. customThe organic layer was collected
13. dry with materialdried with sodium sulfate, gravity
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. customThe compound was purified on a chloroform silica gel column in which the solvent system
17. temperaturewas increased 0.5% MeOH/chloroform every 25 mL of solvent