反应详情

温度

30 °C

N-(3-(5-chloro-2-methoxyphenyl)-1H-pyrazol-4-yl)pyrazolo pyrimidine-3-carboxamide (2.0 g, 5.4 mmol), t-butyl-bromoacetate (0.88 mL, 6.0 mmol), and cesium carbonate (2.1 g, 6.5 mmol) were combined and stirred at 30° C. overnight. The mixture was warmed to 65° C. at which time additional carbonate and t-butylbromoacetate was added and stirred 8 hrs. The mixture was cooled to ambient temperature and stirred overnight, then partitioned EtOAc/water. The organic phase was separated, washed with brine, dried (Na2SO4), filtered through silica gel, and concentrated to a solid. The solid was washed with 1:1 EtOAc/hexanes to yield 1.85 g (71%) of tert-butyl 2-(3-(5-chloro-2-methoxyphenyl)-4-(pyrazolo[1,5-a]pyrimidine-3-carboxamido)-1H-pyrazol-1-yl)acetate as yellow crystals. LCMS (ESI) m+H=483.0. 1H NMR (400 MHz, CDCl3) δ 9.74 (s, 1H), 8.77 (m, 1H), 8.73 (s, 1H), 8.51 (m, 1H0, 8.38 (s, 1H), 8.02 (s, 1H), 7.58 (s, 1H), 7.31 (m, 1H), 6.97 (m, 2H), 4.85 (s, 2H), 3.83 (s, 3H), 1.49 (s, 9H).

1. additionwas added
2. stirringstirred 8 hrs
3. temperatureThe mixture was cooled to ambient temperature
4. stirringstirred overnight
5. customThe organic phase was separated
6. washwashed with brine
7. dry with materialdried (Na2SO4)
8. filtrationfiltered through silica gel
9. concentrationconcentrated to a solid
10. washThe solid was washed with 1:1 EtOAc/hexanes