反应详情

To a solution of 4-(5-amino-2-methylphenyl)-8-(2,6-difluorophenyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one (411.0 mg, 1.0 mmol) in CH2Cl2 (10 mL) at 0° C. was added Et3N (200.0 mg, 2.0 mmol, 2.0 eq), DMAP (5.0 mg, 0.2 mmol, 0.2 eq) and 2-thiophenecarbonyl chloride (292.0 mg, 2.0 mmol, 2.0 eq). After addition the reaction mixture was stirred for about 14 h at ambient temperature. The mixture was concentrated and mixed with H2O (5.0 mL) and EtOAc (20.0 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (3×15 mL). The combined organic phases were washed with saturated aq. NaCl solution, dried over Na2SO4, filtered, and concentrated. Purification via a CombiFlash system (hexane:EtOAc; 4:1) then afforded the title compound: LC-MS m/z 521 (M+H)+, 2.57 min (ret time).

1. additionAfter addition the reaction mixture
2. concentrationThe mixture was concentrated
3. additionmixed with H2O (5.0 mL) and EtOAc (20.0 mL)
4. customThe organic layer was separated
5. extractionthe aqueous layer was extracted with EtOAc (3×15 mL)
6. washThe combined organic phases were washed with saturated aq. NaCl solution
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification via a CombiFlash system (hexane:EtOAc; 4:1)