反应详情

10% Pd/C (0.023 g) was added to methyl 7-benzyloxy-4-(2-cloroethyl)-5-nitro-2-trifluoromethylindole-3-carboxylate (0.0468 g, 0.102 mmol) and chilled THF (7 mL) was added quickly to the 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 completed by TLC. The solution was filtered through Celite pad in a sinter funnel and washed with THF. The amine was then concentrated under reduced pressure and co-evaporated twice with dry CH2Cl2 (2 mL). To the amine were added EDCI (0.040 g, 0.208 mmol) and 5,6,7-trimethoxyindole-2-carboxylic acid (0.026 g, 0.104 mmol). The flask was covered and flushed with N2. The amine was dissolved in dry DMF (10 mL) and stirred for four days under N2. The yellow solution was then diluted with ethyl acetate (100 mL), washed with water three times (100 mL) and 5% NaHCO3 (75 mL). The organic layer was collected, dried with sodium sulfate, gravity filtered and concentrated under reduced pressure. The residue was then purified on a preparative TLC in 2.5% methanol chloroform to yield the crude product. The product was further purified on a preparative TLC in methylene chloride to yield methyl 4-(2-chloroethyl)-7-hydroxy-2-trifluoromethyl-5-(5,6,7-trimethoxyindole-2-carboxamido)indole-3-carboxylate as a yellow solid. Total yield: 0.001 g (0.002 mmol, 2%). TLC (methylene chloride) Rf320.56.500 MHz 1H-NMR (CDCl3): 9.53 (s, 1H), 9.37 (s, 1H), 9.07 (s, 2H), 7.89 (s, 1H), 7.42 (s, 1H), 6.85 (s, 1H), 4.12 (s, 3H), 4.00 (s, 3H), 3.96 (s, 3H), 3.93 (s, 3H), 3.87 (t, 8.0, 2H), 3.72 (t, 8.0, 2H). IR (Neat) 3018, 2965, 2922, 2847, 1729, 1531, 1472, 1344, 1253, 1227, 1178, 1109, 1002, 799.

1. additionwas added quickly to the flask
2. custompurged three times with H2
3. filtrationThe solution was filtered through Celite pad in a sinter funnel
4. washwashed with THF
5. concentrationThe amine was then concentrated under reduced pressure
6. customflushed with N2
7. dissolutionThe amine was dissolved in dry DMF (10 mL)
8. stirringstirred for four days under N2
9. additionThe yellow solution was then diluted with ethyl acetate (100 mL)
10. washwashed with water three times (100 mL) and 5% NaHCO3 (75 mL)
11. customThe organic layer was collected
12. dry with materialdried with sodium sulfate, gravity
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customThe residue was then purified on a preparative TLC in 2.5% methanol chloroform
16. customto yield the crude product
17. customThe product was further purified on a preparative TLC in methylene chloride