反应详情

温度

89 °C

(S)-tert-butyl 4-(tert-butoxycarbonylamino)-5-oxohept-6-enoate (0.94 g) and 2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-amine hydrochloride salt (0.40 g) were dissolved in acetonitrile (4 mL). Diisopropylethylamine (0.52 mL) was added and the mixture wad heated at 89° C. for 25 h. The mixture was cooled to room temperature, diluted with dichloromethane and washed with brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography, on silica gel, eluting with 0.5:99.5 methanol:dichloromethane then 5:95 methanol:dichloromethane to yield (R)-tert-butyl 4-(tert-butoxycarbonylamino)-7-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-ylamino)-5-oxoheptanoate (316 mg) as a beige foam. 1H NMR (CDCl3): 8.25 (m, 1H), 7.40 (m, 2H), 7.30 (m, 1H), 7.17 (m, 1H), 6.98 (m, 1H), 6.47 (m, 1H), 5.20 (m, 1H), 5.00 (m, 1H), 4.22 (m, 1H), 3.59 (m, 2H), 2.90 (m, 2H), 2.32 (m, 2H), 2.10 (m, 1H), 1.83 (m, 1H), 1.45 ppm (s, 18H). MW=619 confirmed by LC-MS, tr=13.23 min (Method Y) MH+=617-621.

1. temperatureThe mixture was cooled to room temperature
2. washwashed with brine
3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe resulting residue was purified by flash column chromatography, on silica gel
7. washeluting with 0.5:99.5 methanol