Reaction Steps
8-(3-Aminophenyl)-2-((2-methoxy-4-morpholinophenyl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one 2,2,2-trifluoroacetate (2b, 63 mg, 0.11 mmol) was treated with DCM (5.0 mL), cooled to 0° C. and treated with DIEA (0.06 mL, 0.34 mmol) and acryloyl chloride (9.16 μL, 0.113 mmol) and stirred at 0° C. for 40 min. The reaction mixture was treated with ice and water and then a saturated solution of NaHCO3. It was extracted with DCM (3×25 mL), dried over Na2SO4, filtered and concentrated. The crude residue was purified on a Gilson prepatory HPLC (Silicycle Silichrome XT C18 column; 30×150 mm, 5μ, 20-95% 0.1% TFA/CH3CN in 0.1% TFA/water) affording N-(3-(2-((2-methoxy-4-morpholinophenyl)amino)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide (2) (26 mg, 0.054 mmol, 47% yield) as a light orange amorphous solid after concentration of the sample containing fractions, treatment with a saturated solution of NaHCO3, extraction with DCM (3×25 mL), drying over Na2SO4, filtration and drying under vacuum. m/z (ESI, +ve ion) 500.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.33 (1H, s), 8.88 (1H, s), 8.04 (1H, d, J=9.6 Hz), 7.66-7.70 (1H, m), 7.64 (1H, d, J=8.2 Hz), 7.45 (1H, t, J=8.0 Hz), 6.94-7.00 (1H, m), 6.90 (1H, d, J=8.6 Hz), 6.67 (1H, d, J=9.6 Hz), 6.59 (1H, d, J=2.5 Hz), 6.42-6.51 (1H, m), 6.40 (1H, dd, J=8.8, 2.5 Hz), 6.22-6.32 (1H, m), 5.77-5.82 (1H, m), 3.71-3.80 (4H, m), 3.63 (3H, s), 3.04-3.14 (4H, m).
