反应详情

5-[3-(2-Dimethylamino-ethylamino)-propyl]-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 23a (5.85 g, 13.8 mmol) was dissolved in 130 ml of toluene under stirring, and added slowly with a solution of trimethyl aluminum in toluene (12 ml, 2 mol/L, 24 mmol) to the solution under an argon atmosphere. Upon the completion of the addition, the reaction mixture was stirred for 10 minutes at room temperature until no white smoke was released, and heated to reflux for 3 hours in an oil bath. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was quenched with ice water. After the reaction system was naturally cooled down to room temperature, the mixture was added with hydrochloric acid solution (50 ml, 2 mol/L) and stirred for 10 minutes. The mixture was adjusted to pH 9 with aqueous sodium hydroxide solution (2 mol/L), and extracted with dichloromethane (50 ml×4). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure to obtain the title compound 5-(2-dimethylamino-ethyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carboxylic acid tert-butyl ester 23b (3.3 g, yield 71.4%) as a yellow solid.

1. additionUpon the completion of the addition
2. stirringthe reaction mixture was stirred for 10 minutes at room temperature until no white smoke
3. temperatureheated
4. temperatureto reflux for 3 hours in an oil bath
5. customthe reaction mixture was quenched with ice water
6. additionthe mixture was added with hydrochloric acid solution (50 ml, 2 mol/L)
7. stirringstirred for 10 minutes
8. extractionextracted with dichloromethane (50 ml×4)
9. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
10. filtrationfiltered
11. customto remove the drying agent
12. concentrationconcentrated under reduced pressure