Reaktion #2316980

Reaktionsgleichung

2-ethoxy-5-(4-ethyl-1-piperazinylsulfonyl)nicotinic acid

water

4-amino-5-ethyl-1-(2-methoxyethyl)-1H-pyrazole-3-carboxamide

→

N-[3-carbamoyl-5-ethyl-1-(2-methoxyethyl)-1H-pyrazol-4-yl}-2-ethoxy-5-(4-ethyl-1-piperazinyl sulfonyl)nicotinamide

Lösungsmittel

ethyl acetate

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturat reflux
2. 2
   workup.ADDITIONwas added to the cooled mixture
3. 3
   workup.STIRRINGthe reaction stirred for a further 17 hours
4. 4
   Temperaturunder reflux
5. 5
   TemperaturThe solution was cooled
6. 6
   TemperaturThe slurry was warmed to 40° C.
7. 7
   EinengenThe organic was concentrated
8. 8
   Sonstigeto by evaporating 0.23 L solvent
9. 9
   TemperaturThe slurry was cooled
10. 10
    Sonstigegranulated at 0-−10° C.
11. 11
    Filtrationfiltered
12. 12
    Waschenthe filter cake was washed with 90% water/10% ethyl acetate, (2 mL/g)

Vorschrift

2-ethoxy-5-(4-ethyl-1-piperazinylsulfonyl)nicotinic acid (27.5 g, 0.08 Mol) was suspended in ethyl acetate (0.193 L) and 1,1-carbonyidimidazole (13.3 g, 0.082 Mol) was added at room temperature. The reaction mixture was heated at 45° C. for 15 minutes and then the reaction was stirred for a further 60 minutes at reflux. After cooling to ambient temperature 4-amino-5-ethyl-1-(2-methoxyethyl)-1H-pyrazole-3-carboxamide (16.5 g, 0.078 Mol) was added to the cooled mixture, and the reaction stirred for a further 17 hours under reflux. The solution was cooled and water (0.07 L) and ethyl acetate (0.17 L) added. The slurry was warmed to 40° C. and the organic separated. The organic was concentrated to by evaporating 0.23 L solvent. The slurry was cooled, granulated at 0-−10° C. filtered and the filter cake was washed with 90% water/10% ethyl acetate, (2 mL/g) to afford N-[3-carbamoyl-5-ethyl-1-(2-methoxyethyl)-1H-pyrazol-4-yl}-2-ethoxy-5-(4-ethyl-1-piperazinyl sulfonyl)nicotinamide as an off white crystalline solid, 38.7 g, 89%. m.p.=159-161° C.

Quelle