反应详情

A mixture of 422 mg (0.95 mmol) of 6-amino-7-{[2-(4-morpholinyl)ethyl]amino}-4-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,4-dihydro-3-quinolinecarbonitrile, 258.7 mg (3.80 mmol) of imidazole in 6 mL of 96% formic acid is refluxed for 6.5 hours. After cooling, the mixture is concentrated under reduced pressure and the residue is diluted with water. Undissolved solid is filtered off and washed with water. The combined filtrate and water washes are brought to pH 8 with 28% ammonium hydroxide aqueous solution. The precipitate is collected by filtration and washed with water. After drying in vacuo, this yields 190.0 mg of the crude product as a yellow solid. The crude product is purified by flash chromatography (elution with methylene chloride, then a gradient of 99:1 to 88:12 methylene chloride/methanol) to give 151.6 mg (49.3%) of the pure product as an off-white solid, mp>270° C.

1. temperatureis refluxed for 6.5 hours
2. temperatureAfter cooling
3. concentrationthe mixture is concentrated under reduced pressure
4. additionthe residue is diluted with water
5. filtrationis filtered off
6. washwashed with water
7. filtrationThe precipitate is collected by filtration
8. washwashed with water
9. customAfter drying in vacuo
10. customThe crude product is purified by flash chromatography (
11. washelution with methylene chloride