تفاعل #68658

معادلة التفاعل

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

المردود 78.5%

المذيبات

acetonitrile

acetonitrile

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   أخرىA 2-L round bottom flask flask equipped with a magnetic stirbar
2. 2
   درجة الحرارةThe stirred slurry was cooled
3. 3
   أخرى3-neck, round bottom flask equipped with a mechanical overhead stirrer and a thermocouple w/adapter
4. 4
   درجة الحرارةcooled to <5 deg C
5. 5
   أخرىThe ice bath was removed
6. 6
   درجة الحرارةto warm
7. 7
   أخرىThe flask was then equipped with a heating mantle and a reflux condenser
8. 8
   درجة الحرارةwas heated
9. 9
   درجة الحرارةto reflux (82 deg C.) for 13 h
10. 10
    درجة الحرارةcooled back to about 60 deg C
11. 11
    ترشيحfiltered through paper
12. 12
    تركيزThe 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
    أخرىthe solids were isolated by vacuum filtration
17. 17
    غسيلwashed with ice-cold 1:1 ACN/H2O (2×150 mL)
18. 18
    أخرىair-dried on the
19. 19
    ترشيحfilter until
20. 20
    أخرىwas obtained (159 g, 78.5% yield)

الإجراء التجريبي

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 (2×150 mL) and air-dried on the filter until a freely flowing solid was obtained (159 g, 78.5% yield).

المصدر