반응 #10568

반응 방정식

tert-butyl N-(2-aminoethyl)carbamate

1-(2-pyridinyl)-4-piperidinylamine dihydrochloride

1,1′-carbonyldiimidazole

N,N-di-iso-propylethylamine

→

title compound

tert-Butyl 2-[({[1-(2-pyridinyl)-4-piperidinyl]amino}carbonyl)amino]ethylcarbamate

용매

acetonitrile

acetonitrile

반응 조건

후처리

1. 1
   온도under reflux for 2.5 hours
2. 2
   온도After cooling to ambient temperature
3. 3
   농축the reaction mixture was concentrated in vacuo
4. 4
   workup.DISSOLUTIONthe residue was dissolved in ethyl acetate (150 ml)
5. 5
   세척This solution was washed successively with saturated aqueous sodium bicarbonate solution (70 ml) and deionised water (20 ml)
6. 6
   추출The aqueous phases were extracted with ethyl acetate (2×100 ml)
7. 7
   세척the combined organic phases were washed with water
8. 8
   건조The organic phase was dried over anhydrous magnesium sulphate
9. 9
   농축the solution was concentrated to a volume of approximately 200 ml in vacuo
10. 10
    workup.DISTILLATIONThe resultant solution was then distilled at atmospheric pressure until the volume
11. 11
    온도to cool to ambient temperature during which time crystallisation
12. 12
    workup.ADDITIONThe resultant thick slurry was diluted with ethyl acetate (60 ml)
13. 13
    온도was cooled in ice
14. 14
    여과The solid was collected by filtration
15. 15
    세척the filter cake was washed with cold ethyl acetate (2×30 ml)
16. 16
    기타The resultant solid was dried in vacuo at 50° C. for 20 hours
17. 17
    기타to give the crude product (24.0 g) that
18. 18
    기타was recrystallised from ethyl acetate (270 ml)

실험 절차

an ice-cooled solution of 1-(2-pyridinyl)-4-piperidinylamine dihydrochloride EP-A-0021973) (20.82 g, 0.0832 moles) and 1,1′-carbonyldiimidazole (14.85 g, 0.915 moles) in acetonitrile (140 ml) under an atmosphere of nitrogen was added N,N-di-iso-propylethylamine (22.0 g, 29.7 ml, 0.170 moles) over a period of 20 minutes. The resultant light brown solution was stirred at ambient temperature for 20 minutes and a solution of tert-butyl N-(2-aminoethyl)carbamate (14.0 g, 0.0874 moles) in acetonitrile (10 ml plus 5 ml rinse) was added over a period of 5 minutes. The resultant mixture was then heated under reflux for 2.5 hours. After cooling to ambient temperature, the reaction mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate (150 ml). This solution was washed successively with saturated aqueous sodium bicarbonate solution (70 ml) and deionised water (20 ml). The aqueous phases were extracted with ethyl acetate (2×100 ml) and the combined organic phases were washed with water. The organic phase was dried over anhydrous magnesium sulphate and the solution was concentrated to a volume of approximately 200 ml in vacuo. The resultant solution was then distilled at atmospheric pressure until the volume was approximately 75 ml. The solution was allowed to cool to ambient temperature during which time crystallisation occurred. The resultant thick slurry was diluted with ethyl acetate (60 ml) and was cooled in ice. The solid was collected by filtration and the filter cake was washed with cold ethyl acetate (2×30 ml). The resultant solid was dried in vacuo at 50° C. for 20 hours to give the crude product (24.0 g) that was recrystallised from ethyl acetate (270 ml) to give the title compound (20.7 g) as a colourless solid.

출처