反应详情

温度

110 °C

Ethyl 3-bromo-1-(1-ethoxyethyl)-1H-thieno[2,3-c]pyrazole-5-carboxylate (10.9 g, 31 mmol), 4-(4-methylpiperazin-1-yl)benzamide (9 g, 41 mmol, 1.3 eq.), copper(I)iodide (0.601 g, 3.1 mmol, 0.1 eq.), preground tripotassium phosphate (20.1 g, 94 mmol, 3 eq.) and 70 mL of anhydrous dioxane degassed beforehand with argon are placed in a 500 mL round-bottomed flask under argon. N,N′-Dimethylethylenediamine (0.336 mL, 3.16 mmol, 0.1 eq.) is added to this suspension by syringe. The reaction mixture is then heated at a temperature in the region of 110° C. for a period of 24 hours. The dioxane is then evaporated off under vacuum and the residue is diluted with ethyl acetate (300 mL) and 150 mL of water. The organic phase is washed with 100 mL of water, dried over magnesium sulfate and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on silica gel, eluting at the start with a dichloromethane/methanol mixture (90/10 by volume). Ethyl 1-(1-ethoxyethyl)-3-[4-(4-methylpiperazin-1-yl)benzoylamino]-1H-thieno[2,3-c]pyrazole-5-carboxylate (4.05 g, 27%) is thus obtained in the form of a pale yellow oil, which product is used directly in the following step.

1. customThe dioxane is then evaporated off under vacuum
2. additionthe residue is diluted with ethyl acetate (300 mL) and 150 mL of water
3. washThe organic phase is washed with 100 mL of water
4. dry with materialdried over magnesium sulfate
5. concentrationconcentrated to dryness under reduced pressure
6. customThe residue is purified by chromatography on silica gel
7. washeluting at the start with a dichloromethane/methanol mixture (90/10 by volume)