反应详情

温度

25 °C

To a solution of 4-(1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzoic acid, (0.637 g, 2.76 mmol) in N,N-dimethylformamide was added 1,1′-carbonyldiimidazole (0.930 g, 5.74 mmol, 2.07 eq.). The resulting solution was stirred at room temperature for 5 hours, whereupon 5-chloro-2-(piperazin-1-ylsulphonyl)-1H-indole (see WO 99/57113, 0.622 g, 2.08 mmol, 1.11 eq.) was added. The reaction mixture was stirred at 25° C. for 14 h and then evaporated in vacuo. The residue was purified by flash column chromatography: first eluting with ethyl acetate:toluene (2:1), then with ethyl acetate. During concentration of the desired fraction, a white solid precipitated. The solid was triturated with hot ethyl acetate (50 mL) to remove a trace of impurity. After drying, pale yellow solid were isolated. De-colorization on charcoal using hot methanol together with the re-crystallization in methanol, gave 0.79 gram 6-{4-[4-(5-chloro-1H-indole-2-sulphonyl)-piperazine-1-carbonyl]-phenyl}-2-methyl-2H-pyridazin-3-one as fine white crystals (yield 56%).

1. additionwas added
2. customevaporated in vacuo
3. customThe residue was purified by flash column chromatography
4. washfirst eluting with ethyl acetate:toluene (2:1)
5. customDuring concentration of the desired fraction, a white solid precipitated
6. customThe solid was triturated with hot ethyl acetate (50 mL)
7. customto remove a trace of impurity
8. customAfter drying
9. custompale yellow solid were isolated
10. customDe-colorization on charcoal using hot methanol together with the re-crystallization in methanol