反应详情

3-chloro-5-{[5-chloro-1-({1-(4-methoxybenzyl)-6-[(4-methoxybenzyl)amino]-1H-pyrazolo[3,4-b]pyridin-3-yl}methyl)-1H-indazol-4-yl]oxy}benzonitrile (0.848 g, 1.228 mmol) was dissolved in TFA (10 mL) and placed in an oil bath at 75° C. After 2.5 hours, the reaction mixture was allowed to cool to room temperature and was concentrated under reduced pressure. The resulting residue was suspended in a chloroform and ethyl acetate mixture (4:1, 200 mL) and aqueous sodium bicarbonate (50 mL) was added. Ethyl acetate was then added until both phases had become solutions. The organic phase was separated and the aqueous phase was washed with chloroform (2×100 mL). The combined organic fractions were dried over MgSO4, filtered and concentrated under reduced pressure. The resulting residue was subjected to automated silica gel chromatography eluting with a gradient of 0-10% methanol in chloroform to yield the title product. 1H NMR (DMSO-d6): δ 12.60 (s, 1H), 7.86 (s, 1H), 7.81-7.78 (m, 1H), 7.73 (d, J=9.0 Hz, 1H), 7.58 (d, J=9.0 Hz, 1H), 7.49-7.47 (m, 1H), 7.38-7.34 (m, 2H), 6.30 (s, 2H), 6.21 (d, J=8.8 Hz, 1H), 5.82 (s, 2H). LRMS (M+1)=449.7

1. customplaced in an oil bath at 75° C
2. concentrationwas concentrated under reduced pressure
3. additionwas added
4. additionEthyl acetate was then added until both phases
5. customThe organic phase was separated
6. washthe aqueous phase was washed with chloroform (2×100 mL)
7. dry with materialThe combined organic fractions were dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. washeluting with a gradient of 0-10% methanol in chloroform