反应详情

To a suspension of tert-butyl (3-(2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate (51) (651 mg, 1.69 mmol) in 10 mL of DCM at RT was added 3 mL of TFA. The resulting homogeneous solution was stirred at RT for 1 h. It was concentrated under reduced pressure. The residue was in dissolved in 20 mL of DCM and cooled with an ice bath, then treated with DEIA (1.47 mL, 8.47 mmol) followed by acryloyl chloride (0.16 mL, 2.03 mmol). After 20 min at 0° C., additional acryloyl chloride (80 μL) was added in. The resulting mixture was stirred for 5 min, then quenched with 0.5 N NaOH (10 mL). The layers were separated and the water layer was extracted with 50 mL of DCM. The combined DCM extracts were washed with 2×5 mL of brine, dried over Na2SO4 and concentrated. The residue was stirred in 25 mL of EtOAc. The insoluble solid was filtered and dried to give 310 mg of N-(3-(2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide (11a). The filtrate was concentrated and purified on a silica gel column (35-100% EtOAc in hexanes) to give 140 mg of N-(3-(2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide (11a). m/z (ESI, +ve ion) 338.9 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.40 (1H, s), 8.95 (1H, s), 8.05 (1H, d, J=9.6 Hz), 7.68 (2H, m), 7.49 (1H, t, J=7.8 Hz), 7.04 (1H, d, J=8.2 Hz), 6.72 (1H, d, J=9.6 Hz), 6.46 (1H, dd, J=17.0, 10.2 Hz), 6.26 (1H, d, J=16.8 Hz), 5.78 (1H, d, J=9.6 Hz), 2.20 (3H, s).

1. concentrationIt was concentrated under reduced pressure
2. dissolutionin dissolved in 20 mL of DCM
3. temperaturecooled with an ice bath
4. additiontreated with DEIA (1.47 mL, 8.47 mmol)
5. waitAfter 20 min at 0° C.
6. stirringThe resulting mixture was stirred for 5 min
7. customquenched with 0.5 N NaOH (10 mL)
8. customThe layers were separated
9. extractionthe water layer was extracted with 50 mL of DCM
10. washThe combined DCM extracts were washed with 2×5 mL of brine
11. dry with materialdried over Na2SO4
12. concentrationconcentrated
13. stirringThe residue was stirred in 25 mL of EtOAc
14. filtrationThe insoluble solid was filtered
15. customdried