反应详情

Tert-butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-(methylsulfonyloxy)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (155 mg, 0.218 mmol) in DMF was added NaCN (21.37 mg, 0.436 mmol) and the reaction was stirred at R.T for 1 h. LC/MS showed no reaction. The reaction was heated at 50 C for another hour, LC/MS showed no reaction either. The reaction was again heated at 80 C for another hour, no reaction was observed. It was stirred at 80 C over the weekend. LC/MS showed product along with staring material. It was stirred at 80 C for 6 h, LC/MS showed the reaction was complete. The reaction was then partitioned between Et2O and H2O, the phase was separated and the aqueous phase was extracted with Et2O, the combined organic phases were washed with water and brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. It was purified by Biotage LC (30% EtOAc/Hex) to title compound (52.2 mg, 0.081 mmol, 37.3% yield). 1H-NMR (CDCl3, 300 MHz) δ 8.0 (s, 1H),), 7.53 (m, 1H), 7.32 (m, 2H), 7.05 (m, 2H), 6.63 (s, 1H), 5.61 (s, 2H), 5.04 (m, 1H), 3.68 (m, 2H), 3.57 (t, J=8.05 Hz, 2H), 3.45 (m, 2H), 3.05-2.96 (m, 3H), 2.74 (m, 1H), 2.28 (m, 1H), 1.98 (m, 1H), 1.96 (m, 1H), 1.83 (m, 1H), 1.42 (s, 9H), 0.9 (t, J=8.42 Hz, 2H); 13C-NMR (CDCl3, 126 MHz) δ 161.63 (d, J=245.7 Hz), 155.0, 144.8, 129.9, 128.9, 128.0, 124.0, 122.8, 119.3, 117.2, 115.5, 115.4, 81.9, 79.5, 79.0, 73.4, 67.8, 42.5, 41.4, 32.4, 28.6, 25.3, 17.9, 1.35. LC/MS (HPLC method 3): tR=4.16 min, 643.1 (MH)+.

1. customno reaction
2. temperatureThe reaction was heated at 50 C for another hour
3. customno reaction either
4. temperatureThe reaction was again heated at 80 C for another hour
5. stirringIt was stirred at 80 C over the weekend
6. stirringIt was stirred at 80 C for 6 h
7. customThe reaction was then partitioned between Et2O and H2O
8. customthe phase was separated
9. extractionthe aqueous phase was extracted with Et2O
10. washthe combined organic phases were washed with water and brine
11. dry with materialdried over magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure