反应详情

温度

80 °C

To 3-chloro-5-{1-[(3-methyl phenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-4-pyridinecarbonitrile (100 mg, 0.258 mmol) in Ethanol (6 mL) was added hydrazine monohydrate (1 mL, 31.9 mmol), and the reaction mixture was stirred at 80° C. overnight into a sealed vessel. LCMS analysis of the reaction mixture indicated the presence of starting material. Therefore, the reaction mixture was stirred at 100° C. overnight. The mixture was poured onto EtOAc and water. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. The resulting residue was purified by flash chromatography on SiO2 (gradient: 100% Hexanes to 100% EtOAc to 20% CH3OH/EtOAc). The fractions containing the product were combined, concentrated, and triturated with Et2O to afford 4-{1-[(3-methyl phenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-1H-pyrazolo[3,4-c]pyridin-3-amine (15 mg) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 2.32 (s, 3H), 3.25 (t, J=8.34 Hz, 2H), 3.85 (s, 2H), 4.24 (t, J=8.46 Hz, 2H), 4.6 (m, 1.3H(NH2)), 7.05-7.16 (m, 3H), 7.19-7.28 (m, 1H), 7.33 (d, J=8.34 Hz, 1H), 7.42 (s, 1H), 7.93 (s, 1H), 8.21 (d, J=8.34 Hz, 1H), 8.74 (s, 1H), 12.27 (br. s., 1H).

1. stirringTherefore, the reaction mixture was stirred at 100° C. overnight
2. customThe organic layer was separated
3. washwashed with brine
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customThe resulting residue was purified by flash chromatography on SiO2 (gradient: 100% Hexanes to 100% EtOAc to 20% CH3OH/EtOAc)
8. additionThe fractions containing the product
9. concentrationconcentrated
10. customtriturated with Et2O