تفاعل #157979

معادلة التفاعل

Tert-butyl[(4-methylpiperidin-4-yl)methyl]carbamate

DIPEA

NMP

11-chloro-2,3-dihydro-1H-cyclopenta[4,5]pyrido[1,2-a]benzimidazole-4-carboxamide

→

11-[4-(aminomethyl)-4-methylpiperidin-1-yl]-2,3-dihydro-1H-cyclopenta[4,5]pyrido[1,2-a]benzimidazole-4-carboxamide dihydrochloride

المردود 78.5%

المذيبات

water

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةheating
2. 2
   أخرىwere performed at 200° C. for 60 minutes under microwave irradiation
3. 3
   أخرىto the reaction liquid
4. 4
   ترشيحthe resulting precipitate was collected by filtration
5. 5
   أخرىdried under reduced pressure
6. 6
   workup.ADDITIONTFA was then added
7. 7
   workup.STIRRINGstirring
8. 8
   أخرىThe reaction liquid
9. 9
   تركيزwas concentrated under reduced pressure
10. 10
    أخرىthe residue was purified by silica gel column chromatography (MeOH/chloroform)
11. 11
    أخرىThe resulting crude purified matter
12. 12
    workup.DISSOLUTIONwas dissolved in chloroform
13. 13
    workup.ADDITIONa 4 M hydrochloric acid-EtOAc solution was then added
14. 14
    workup.STIRRINGstirring
15. 15
    workup.WAITwas performed at room temperature for 1 hour
16. 16
    تركيزThe solvent was concentrated under reduced pressure

الإجراء التجريبي

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).

المصدر