反应详情

温度

40 °C

A solution of 4-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid (2.25 g, 12 mmol), 1-(3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride (2.87 g, 15 mmol), DMAP (1.83 g, 15 mmol), and DMF (10 mL) in dichloromethane (40 mL) is stirred under nitrogen at 20° C. for 2 hours. 6-(3-Diethylamino-propoxy)-pyridin-3-ylamine (2.50 g, 11.2 mmol) is added. The mixture is stirred under nitrogen at 40° C. for 24 hours; and then poured into 10% NaCl, treated with 1 M sodium carbonate to pH 10, and extracted with chloroform (100 mL). The solution is concentrated, diluted with xylenes (100 mL), and the volatiles are thoroughly evaporated under reduced pressure. The residue is purified by column chromatography on silica gel using a mixture of chloroform-methanol-30% ammonium hydroxide (90:9:1, v/v/v) as an eluent and the residue is recrystallized from ethyl acetate to give pure 4-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid [6-(3-diethylamino-propoxy)-pyridin-3-yl]-amide. 1H NMR (CD3OD) t, J=7.1 Hz, 6H), 1.97 (m, 2H), 2.25 (quintet, J=6.3 Hz, 2H), 2.62 (q, J=7.1 Hz, 4H), 2.71 (m, 4H), 2.99 (t, J=6.3 Hz, 2H), 4.03 (t, J=6.3 Hz, 2H), 6.81 (dd, J=8.9 and 0.5 Hz, 1H), 8.12 (dd, J=8.9 and 2.7 Hz, 1H), 8.56 (dd, J=2.7 and 0.5 Hz, 1H). MW 385.471; MS (M−H)− 384.

1. extractionextracted with chloroform (100 mL)
2. concentrationThe solution is concentrated
3. additiondiluted with xylenes (100 mL)
4. customthe volatiles are thoroughly evaporated under reduced pressure
5. customThe residue is purified by column chromatography on silica gel using
6. additiona mixture of chloroform-methanol-30% ammonium hydroxide (90:9:1, v/v/v) as an eluent
7. customthe residue is recrystallized from ethyl acetate