反应详情

A solution of tert-butyl 4-(3-iodo-1H-indazol-5-yl)piperidine-1-carboxylate (218. mg; 0.51 mmol; 1.0 eq.), di-tert-butyldicarboxylate (145 mg; 0.66 mmol; 1.3 eq.), diméthylamino-4-pyridine (12.5 mg; 0.10 mmol; 0.20 eq.) and TEA (86.0 μl; 0.61 mmol; 1.2 eq.) in acetonitrile (6.5 mL) was stirred at RT O/N. Acetonitrile was removed under reduced pressure, the residue was diluted with water and extracted three times with Ether. Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude was purified by flash chromatography on silica (heptane/EtOAc, gradient from 90:10 to 75:25) to give the title compound as a colorless oil (200 mg, 74%). 1H NMR (300 MHz, DMSO-d6) δ 7.99 (d, J=8.7 Hz, 1H), 7.62 (dd, J=1.6, 8.7 Hz, 1H), 7.35 (s, 1H), 4.18-4.03 (m, 2H), 2.96-2.73 (m, 3H), 1.87-1.75 (m, 2H), 1.64 (s, 9H). 1.61-1.48 (m, 2H), 1.42 (s, 9H). (Condition A): Rt 6.33 min (purity 99.8%).

1. customAcetonitrile was removed under reduced pressure
2. additionthe residue was diluted with water
3. extractionextracted three times with Ether
4. washCombined organic phases were washed with brine
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude was purified by flash chromatography on silica (heptane/EtOAc, gradient from 90:10 to 75:25)