反应详情

Under a nitrogen atmosphere, a solution of 5-(tert-butoxycarbonylamino)valeric acid (1.50 g, 6.91 mmol) in dichloroethane (30 mL) was cooled to −25° C. Triethylamine (2.40 mL, 17.2 mmol) and pivaloyl chloride (0.85 mL, 6.91 mmol) were added, and the reaction was stirred for three hours, during which time the temperature rose to −10° C. 7-Benzyloxy-N4-(2-phenoxyethyl)quinoline-3,4-diamine (0.850 g, 2.20 mmol), prepared as described in Parts A-B of Example 46, was added in one portion followed by a small scoop of 4-dimethylaminopyridine. The reaction was allowed to warm to room temperature and stirred overnight and then heated at reflux for three hours. The reaction solution was washed with saturated sodium bicarbonate, water (2×), and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluting with sequentially with 98:2 and 95:5 chloroform:methanol) to yield a solid. The solid was treated with diethyl ether and concentrated under reduced pressure to provide 1.03 g of tert-butyl {4-[7-benzyloxy-1-(2-phenoxyethyl)-1H-imidazo[4,5-c]quinolin-2-yl]butyl}carbamate as a white powder.

1. customrose to −10° C
2. additionwas added in one portion
3. stirringstirred overnight
4. temperatureheated
5. temperatureat reflux for three hours
6. washThe reaction solution was washed with saturated sodium bicarbonate, water (2×), and brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe crude product was purified by column chromatography on silica gel (
11. washeluting with sequentially with 98:2 and 95:5 chloroform
12. custommethanol) to yield a solid
13. concentrationconcentrated under reduced pressure