Reaktion #306435

Reaktionsgleichung

polyethylene

hydrazine

4-methylbenzenesulfonic acid hydrate

di(1H-imidazol-1-yl)methanone

N-Boc glycine

1-(6-chloropyridazin-3-yl)hydrazine

→

tert-butyl (6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate

Ausbeute 78.5%

Lösungsmittel

acetonitrile

acetonitrile

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeA 2-L round bottom flask flask equipped with a magnetic stirbar
2. 2
   TemperaturThe stirred slurry was cooled
3. 3
   Sonstige3-neck, round bottom flask equipped with a mechanical overhead stirrer and a thermocouple w/adapter
4. 4
   Temperaturcooled to <5 deg C
5. 5
   SonstigeThe ice bath was removed
6. 6
   Temperaturto warm
7. 7
   SonstigeThe flask was then equipped with a heating mantle and a reflux condenser
8. 8
   Temperaturwas heated
9. 9
   Temperaturto reflux (82 deg C.) for 13 h
10. 10
    Temperaturcooled back to about 60 deg C
11. 11
    Filtrationfiltered through paper
12. 12
    EinengenThe brown filtrate was then concentrated by rotary evaporation
13. 13
    workup.STIRRINGThe resulting thick yellow-brown slurry was stirred in an ice bath
14. 14
    workup.ADDITIONdiluted with ACN (about 100 mL)
15. 15
    workup.STIRRINGAfter stirring for 1 h
16. 16
    Sonstigethe solids were isolated by vacuum filtration
17. 17
    Waschenwashed with ice-cold 1:1 ACN/H2O (2×1 50 mL)
18. 18
    Sonstigeair-dried on the
19. 19
    Filtrationfilter until
20. 20
    Sonstigewas obtained (159 g, 78.5% yield)

Vorschrift

A 2-L round bottom flask flask equipped with a magnetic stirbar was charged with di(1H-imidazol-1-yl)methanone (121 g, 749 mmol) and acetonitrile (500 mL). The stirred slurry was cooled by immersing the flask in an ice bath. A solution of N-Boc glycine (125 g, 714 mmol) in acetonitrile (500 mL) was added via a 500-mL addition funnel over the course of 30-45 min. The mixture was aged for 1 h while a 5-L, 3-neck, round bottom flask equipped with a mechanical overhead stirrer and a thermocouple w/adapter was charged with 1-(6-chloropyridazin-3-yl)hydrazine (108 g, 749 mmol) and acetonitrile (900 mL) and cooled to <5 deg C. in an ice bath. The cold solution of the acylimidazole was then transferred via a polyethylene cannula into the thick suspension of the hydrazine over a period of 30-45 min). The ice bath was removed, and the mixture was allowed to warm. After 2.5 h of stirring, 4-methylbenzenesulfonic acid hydrate (143 g, 749 mmol) was added. The flask was then equipped with a heating mantle and a reflux condenser and was heated to reflux (82 deg C.) for 13 h, then cooled back to about 60 deg C. At this point, the warm solution was vacuum filtered through paper. The brown filtrate was then concentrated by rotary evaporation. The resulting thick yellow-brown slurry was stirred in an ice bath and diluted with ACN (about 100 mL). After stirring for 1 h, the solids were isolated by vacuum filtration, washed with ice-cold 1:1 ACN/H2O (2×1 50 mL) and air-dried on the filter until a freely flowing solid was obtained (159 g, 78.5% yield).

Quelle