反应详情

Tert-butyl[(4-methylpiperidin-4-yl)methyl]carbamate (343 mg), and DIPEA (348 μl) were added to an NMP (3 ml) solution of 11-chloro-2,3-dihydro-1H-cyclopenta[4,5]pyrido[1,2-a]benzimidazole-4-carboxamide (286 mg), and heating and stirring were performed at 200° C. for 60 minutes under microwave irradiation. After adding water to the reaction liquid, the resulting precipitate was collected by filtration and dried under reduced pressure. The resulting solid was suspended in chloroform, TFA was then added thereto and stirring was performed at room temperature for 1 hour. The reaction liquid was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (MeOH/chloroform). The resulting crude purified matter was dissolved in chloroform, a 4 M hydrochloric acid-EtOAc solution was then added thereto and stirring was performed at room temperature for 1 hour. The solvent was concentrated under reduced pressure and the residue was solidified using EtOH/Et2O to obtain 11-[4-(aminomethyl)-4-methylpiperidin-1-yl]-2,3-dihydro-1H-cyclopenta[4,5]pyrido[1,2-a]benzimidazole-4-carboxamide dihydrochloride (177 mg).

1. temperatureheating
2. customwere performed at 200° C. for 60 minutes under microwave irradiation
3. customto the reaction liquid
4. filtrationthe resulting precipitate was collected by filtration
5. customdried under reduced pressure
6. additionTFA was then added
7. stirringstirring
8. customThe reaction liquid
9. concentrationwas concentrated under reduced pressure
10. customthe residue was purified by silica gel column chromatography (MeOH/chloroform)
11. customThe resulting crude purified matter
12. dissolutionwas dissolved in chloroform
13. additiona 4 M hydrochloric acid-EtOAc solution was then added
14. stirringstirring
15. waitwas performed at room temperature for 1 hour
16. concentrationThe solvent was concentrated under reduced pressure