反应详情

To a solution of (4-{3-tert-butyl-5-[({[4-(pyridin-4-yloxy)phenyl]amino}-carbonyl)amino]-1H-pyrazol-1-yl}phenyl)acetic acid (100 mg, 0.21 mmol) in THF (4 mL) was added borane-methyl sulfite complex (0.51 mL, 2M in THF) drop-wise with stirring at room temperature. The resulting reaction mixture was heated at reflux for 2 h, then cooled to room temperature and quenched by the addition of EtOH/1N HCl. The resulting mixture was heated at reflux for 1 h. The mixture was cooled to room temperature and evaporated at reduced pressure, and the residue was dissolved in a mixture of EtOAc and saturated NaHCO3. The organic phase was dried over Na2SO4, concentrated, and purified by MPLC (50:50 hexane/EtOAc). The desired product was obtained as a white solid (50 mg) in 51% yield. 1H-NMR (DMSO-d6) δ 9.12 (s, 1H), 8.39 (m, 3H), 7.48 (d, J=9.0 Hz, 2H), 7.40-7.33 (m, 4H), 7.07 (d, J=8.8 Hz, 2H), 6.85 (m, 2H), 6.34 (s, 1H), 4.69 (t, J=5.1 Hz, 1H), 3.64 (m, 2H), 2.78 (t, J=7.1 Hz, 2H), 1.27 (s, 9H); MS LC-MS [M+H]+=472.2, RT=2.35 min.

1. customThe resulting reaction mixture
2. temperaturewas heated
3. temperatureat reflux for 2 h
4. temperaturecooled to room temperature
5. customquenched by the addition of EtOH/1N HCl
6. temperatureThe resulting mixture was heated
7. temperatureat reflux for 1 h
8. temperatureThe mixture was cooled to room temperature
9. customevaporated at reduced pressure
10. dissolutionthe residue was dissolved in a mixture of EtOAc and saturated NaHCO3
11. dry with materialThe organic phase was dried over Na2SO4
12. concentrationconcentrated
13. custompurified by MPLC (50:50 hexane/EtOAc)