Reaktion #719727

Reaktionsgleichung

HCl

HCl

9H-fluoren-9-ylmethyl({[2-({4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)ethyl]amino}sulfonyl)carbamate

THF

N,N-bis(2-aminoethyl)ethane-1,2-diamine

→

crude desired product

Ausbeute 90.3%

4-({2-[(Aminosulfonyl)amino]ethyl}amino)-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide

Ausbeute 90.3%

Lösungsmittel

tert-butyl methyl ether

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeto produce a homogeneous solution
2. 2
   workup.ADDITIONwas added dropwise over 35 minutes via an addition funnel
3. 3
   WaschenThe addition funnel was rinsed with anhydrous THF (50 mL)
4. 4
   workup.ADDITIONthe rinse was added to the reaction mixture
5. 5
   SonstigeThe cold bath was removed
6. 6
   workup.ADDITIONEtOAc (400 mL) was added
7. 7
   Sonstigethe resulting mixture was transferred to a 2 L 4-neck round bottom flask
8. 8
   Temperaturcooled to about 0-5° C. in an ice bath
9. 9
   Temperaturwhile maintaining the internal temperature at below 10° C
10. 10
    SonstigeThe two phases were separated
11. 11
    Extraktionthe aqueous phase was extracted with EtOAc (200 mL)
12. 12
    Temperaturcooled to about 6-7° C
13. 13
    Temperaturmaintaining the internal temperature at below 10° C
14. 14
    SonstigeThe two phases were separated
15. 15
    Waschenthe organic phase was washed with water (2×400 mL)
16. 16
    Trocknendried over MgSO4
17. 17
    Einengenconcentrated under reduced pressure to a light yellow syrup
18. 18
    workup.DISSOLUTIONThe syrup was dissolved in EtOAc (60.0 mL)
19. 19
    Sonstigeto yield a homogeneous solution
20. 20
    workup.STIRRINGThe resulting slurry was stirred overnight at room temperature
21. 21
    Temperaturcooled in an ice bath for 1 h
22. 22
    FiltrationThe solids were collected by filtration
23. 23
    Waschenwashed with an ice cold 250 mL solution of DCM (150 mL) and TBME (100 mL)
24. 24
    Sonstigedried under vacuum

Vorschrift

Into a 1 L 4-neck round bottom flask was charged 9H-fluoren-9-ylmethyl({[2-({4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)ethyl]amino}sulfonyl)carbamate (25.0 g, 36.4 mmol) and anhydrous THF (250 mL) at ambient temperature to produce a homogeneous solution. The solution was then cooled to 0-5° C. in an ice bath before N,N-bis(2-aminoethyl)ethane-1,2-diamine (114 mL, 728 mmol) was added dropwise over 35 minutes via an addition funnel. The addition funnel was rinsed with anhydrous THF (50 mL) and the rinse was added to the reaction mixture. The cold bath was removed and the reaction was gradually warmed to ambient temperature and stirred at ambient temperature for 2.5 h. EtOAc (400 mL) was added and the resulting mixture was transferred to a 2 L 4-neck round bottom flask and cooled to about 0-5° C. in an ice bath. A solution of 2.0 M aqueous HCl (400 mL, 800.0 mmol) was added dropwise via an addition funnel, while maintaining the internal temperature at below 10° C. The two phases were separated and the aqueous phase was extracted with EtOAc (200 mL). The organic fractions were combined and cooled to about 6-7° C. A solution of 2.0 M aqueous HCl (200.0 mL, 400.0 mmol) was added dropwise to the cold organic fraction, maintaining the internal temperature at below 10° C. The two phases were separated and the organic phase was washed with water (2×400 mL), dried over MgSO4, and concentrated under reduced pressure to a light yellow syrup. The syrup was dissolved in EtOAc (60.0 mL) to yield a homogeneous solution. To the solution was added a solution of DCM (250.0 mL) and tert-butyl methyl ether (TBME, 100.0 mL) dropwise. The resulting slurry was stirred overnight at room temperature, then cooled in an ice bath for 1 h. The solids were collected by filtration, washed with an ice cold 250 mL solution of DCM (150 mL) and TBME (100 mL), and dried under vacuum to give 14.4 g of the crude desired product as white solids.

Quelle