反应详情

温度

75 °C

6-Bromo-N′-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]acetyl}-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carbohydrazide (950 mg, 1.683 mmol) was dried over phosphorus pentoxide in a desicator overnight. 6-bromo-N′-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]acetyl}-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carbohydrazide (950 mg, 1.683 mmol) and methoxycarbonylsulfamoyl)triethylammonium hydroxide (602 mg, 2.52 mmol) were suspended in anhydrous tetrahydrofuran (20 ml) and heated to 75° C. for 2 h. The solvent was removed in vacuo and the residue partitioned between dichloromethane (15 ml) and saturated sodium bicarbonate solution (15 ml). The layers were separated (hydrophobic frit), the aqueous washed with further dichloromethane (5 ml) and the combined organics concentrated in vacuo to give a yellow solid. This was purified by column chromatography, loading in dichloromethane onto a silica cartridge 50 g, using a 0-100% ethyl acetate-cyclohexane over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white solid (680 mg).

1. customThe solvent was removed in vacuo
2. customthe residue partitioned between dichloromethane (15 ml) and saturated sodium bicarbonate solution (15 ml)
3. customThe layers were separated (hydrophobic frit)
4. washthe aqueous washed with further dichloromethane (5 ml)
5. concentrationthe combined organics concentrated in vacuo
6. customto give a yellow solid
7. customThis was purified by column chromatography, loading in dichloromethane onto a silica cartridge 50 g
8. customover 40 mins
9. customevaporated in vacuo