反应详情

温度

-78 °C

To a solution of 6-(4-chlorophenoxy)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (110 mg, 0.25 mmol) in THF (5 mL) at −78° C. was added LDA (2.0 M in THF, 0.63 mL, 1.25 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then a solution of 4-fluorobenzaldehyde (62 mg, 0.50 mmol) in THF (1 mL) was added dropwise. The reaction was stirred at −78° C. for 1 h, quenched with sat. aq. NH4Cl (5 mL) then diluted with EA (30 mL) and water (30 mL). The organic layer was dried over Na2SO4 and concentrated to give a residue which was purified by chromatography eluted with PE/EA (7:1) to give 6-(4-chlorophenoxy)-5-((4-fluorophenyl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (55 mg, 40% yield) as a solid. LCMS: [M++Na] 592 and TR=3.372 min.

1. stirringThe reaction was stirred at −78° C. for 1 h
2. customquenched with sat. aq. NH4Cl (5 mL)
3. additionthen diluted with EA (30 mL) and water (30 mL)
4. dry with materialThe organic layer was dried over Na2SO4
5. concentrationconcentrated
6. customto give a residue which
7. customwas purified by chromatography
8. washeluted with PE/EA (7:1)