反应详情

温度

25 °C

2,2,2-Trifluoroacetic acid (0.7 mL, 9.09 mmol) was added dropwise to tert-butyl 4-((5-(6-(bis(4-methoxybenzyl)amino)-2-methylpyrimidin-4-yl)-6-fluoropyridin-3-yl)methyl)piperazine-1-carboxylate (64.3 mg, 0.100 mmol) in dichloromethane (1.0 mL) at 25° C., and the resulting solution was stirred at 25° C. for 30 min. The reaction mixture was then concentrated in vacuo, and the residue was taken up in DCM (3.0 mL) and cooled to 0° C. Triethylamine (0.105 mL, 0.750 mmol) was added to the resulting solution, immediately followed by methanesulfonyl chloride (0.015 mL, 0.200 mmol). The resulting mixture was stirred at 0° C. for 20 min and then was concentrated onto silica gel and chromatographically purified (ISCO, 4 g, 0 to100% (10% MeOH-EtOAc)/hexanes) to provide 6-(2-fluoro-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-2-methylpyrimidin-4-amine (54.5 mg, 0.088 mmol, 88% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.45 (d, J=9.39 Hz, 1H); 8.14 (s, 1H); 7.17 (d, J=6.85 Hz, 4H); 6.86 (d, J=8.80 Hz, 5H); 4.74 (br. s., 4H); 3.79 (s, 6H); 3.60 (s, 2H); 3.25 (br. s., 4H); 2.78 (s, 3H); 2.62 (s, 3H); 2.58 (br. s., 4H). 19F NMR (377 MHz, CDCl3) 6-70.62 (d, J=8.01 Hz, 1 F). m/z (ESI, +ve ion) 621.1 (M+H)+.

1. concentrationThe reaction mixture was then concentrated in vacuo
2. temperaturecooled to 0° C
3. stirringThe resulting mixture was stirred at 0° C. for 20 min
4. concentrationwas concentrated onto silica gel
5. customchromatographically purified (ISCO, 4 g, 0 to100% (10% MeOH-EtOAc)/hexanes)