反应详情

To a stirred suspension of 3-iodoaniline (1.27 mL, 1 mmol) in anhydrous toluene (100 mL) in a pre-dried flask under N2 atmosphere was added trimethylaluminium (6.1 mL of a 2M solution in toluene, 12.0 mmol), and the resulting solution left to stir at rt overnight. Methyl 3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxylate (3.0 g, 10 mmol) was then added and the mixture heated at reflux for 5 h. Upon cooling to rt, 100 mL of 2M NaOH was added and the mixture was stirred for 30 min. The solution was then partitioned over CH2Cl2 and the aqueous phase was extracted with CH2Cl2 (3×100 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The resulting brown solid was treated with MeOH, sonicated for 2 min, and filtered. The solid was washed with MeOH to provide 3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxylic acid (3-iodophenyl)amide as a brown powder. MS (ES): m/z 485.8 [M+1]. 1H NMR (DMSO-d6, 400 MHz): δ5.06 (d, J=5.4 Hz, 2H), 6.77 (d, J=5.6 Hz, 1H), 7.08 (t, J=8.0 Hz, 1H), 7.37 (d, J=6.0 Hz, 2H), 7.60 (d, J=5.6 Hz, 1H), 7.66-7.69 (m, 2H), 7.78 (t, J=7.6 Hz, 1H), 8.04 (d, J=8.4 Hz, 1H), 8.04-8.10 (m, 1H), 8.19 (s, 1H), 8.22 (d, J=8.8 Hz, 1H), 8.82 (d, J=4.4 Hz, 1H), 9.47 (s, 1H).

1. waitleft
2. temperaturethe mixture heated
3. temperatureat reflux for 5 h
4. temperatureUpon cooling to rt
5. stirringthe mixture was stirred for 30 min
6. customThe solution was then partitioned over CH2Cl2
7. extractionthe aqueous phase was extracted with CH2Cl2 (3×100 mL)
8. dry with materialThe combined organic extracts were dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. additionThe resulting brown solid was treated with MeOH
12. customsonicated for 2 min
13. filtrationfiltered
14. washThe solid was washed with MeOH