反应详情

As an alternate procedure to the compound described in Example 9, a solution of 3-(2-chloro-5-methylpyrimidin-4-yl)-1H-indole (INTERMEDIATE 1, 3.39 g, 13.9 mmol), 2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)aniline (INTERMEDIATE 27, 4.23 g, 13.89 mmol), and PTSA monohydrate (6.61 g, 34.74 mmol) in n-pentanol (56 mL) was heated in an oil bath at 140° C. overnight. The reaction mixture was allowed to cool to RT. Hunig's base (10 mL) was added. Solvent was removed in vacuo and to the residue was added methanol (500 mL). Silica gel (120 g) was added to the mixture. Concentration in vacuo removed the solvent, and the residue was loaded to silica gel column and eluted with 10% MeOH, 1% NH4OH in CH2Cl2. The collected fractions were concentrated and the residue was triturated with diethyl ether. Filtration afforded the solid and it was dissolved in a mixture of CH2Cl2 (100 mL) and MeOH (500 mL). Concentration in vacuo reduced the solvent volume to 70 mL and filtration yielded the solid as the title compound (3.8 g, 54% yield).

1. customSolvent was removed in vacuo and to the residue
2. additionwas added methanol (500 mL)
3. additionSilica gel (120 g) was added to the mixture
4. concentrationConcentration in vacuo
5. customremoved the solvent
6. washeluted with 10% MeOH, 1% NH4OH in CH2Cl2
7. concentrationThe collected fractions were concentrated
8. customthe residue was triturated with diethyl ether
9. filtrationFiltration
10. customafforded the solid and it
11. concentrationConcentration in vacuo
12. filtrationto 70 mL and filtration