反应详情

温度

100 °C

To a suspension of 2-methoxy-4-(4-methylpiperazin-1-yl)aniline (Green Chempharm; 3.45 g, 15.57 mmol) and N-(3-(5-methyl-2-(methylsulfinyl)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide (5b) (4.59 g, 12.46 mmol) in anhydrous tert-butanol (40 mL) and dioxane (5 mL) at RT was added DIEA (4.33 mL, 24.92 mmol). The mixture was heated at 100° C. for 40 h. The reaction mixture was concentrated under reduced pressure (rotary evaporator) to remove the volatiles and the resulting crude residue was suspended in Et2O and filtered. The greenish-brown amorphous solid was washed with Et2O (3×50 mL) and this removed most of the remaining aniline starting material. The crude material was dry-packed on silica gel and purified on a silica gel column (1-20% MeOH in DCM) affording N-(3-(2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide (5) (2.03 g, 3.86 mmol, 31% yield) as a yellow amorphous solid. m/z (ESI, +ve ion) 526.2 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.33 (1H, s), 8.80 (1H, s), 8.09 (1H, s), 7.88 (1H, d, J=8.2 Hz), 7.56 (1H, J=1.9 Hz), 7.50 (1H, t, 1=8.1 Hz), 7.27 (1H, d, J=8.8 Hz), 6.97 (1H, dt, J=6.9, 1.0 Hz), 6.52 (1H, d, J=2.5 Hz), 6.37-6.48 (1H, m), 6.29-6.35 (1H, m), 6.19-6.29 (1H, m), 6.01 (1H, br. s.), 5.71-5.80 (1H, m), 3.78 (3H, s), 3.02 (4H, br. s.), 2.46 (3H, s), 2.43 (4H, t, J=4.9 Hz), 2.22 (3H, s).

1. concentrationThe reaction mixture was concentrated under reduced pressure (rotary evaporator)
2. customto remove the volatiles
3. filtrationfiltered
4. washThe greenish-brown amorphous solid was washed with Et2O (3×50 mL)
5. customthis removed most of the remaining aniline starting material
6. custompurified on a silica gel column (1-20% MeOH in DCM)