Diisopropylethylamine → 5-Chloro-4-(1H-indol-3-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-2-amine

Participants

Reaction Steps

As an alternate procedure to the compound described in Example 10, a solution of 3-(2,5-dichloropyrimidin-4-yl)-1H-indole (INTERMEDIATE 2) (3.67 g, 13.89 mmol), 2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)aniline (INTERMEDIATE 27) (4.23 g, 13.89 mmol), and PTSA monohydrate (6.6 g, 34.7 mmol) in n-pentanol (56 mL) was heated in an oil bath at 140° C. overnight. The reaction mixture was cooled to RT. Hunig's base (10 mL) was added. 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 (3.9 g, 53% yield).

Provenance & Evidence