反应详情

温度

-78 °C

To a solution of 6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 36, step 3, 150 mg, 0.4 mmol) in THF (6 mL) at −78° C. was added LDA (2M in THF, 1.0 mL, 2.0 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then 3-methylbutanal (68.8 mg, 0.8 mmol) in THF (1.5 mL) was added. The reaction was stirred at −78° C. for 1 h, quenched with aq. NH4Cl (5 mL) diluted with water (13 mL) then extracted with EA (30 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by Prep TLC eluted with PE/EA (2:1) to give 5-(1-hydroxy-3-methylbutyl)-6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (60 mg, 32.4% yield) as a white solid. LCMS: [M+-THP-OH] 362 and TR=2.616 min.

1. stirringThe reaction was stirred at −78° C. for 1 h
2. customquenched with aq. NH4Cl (5 mL)
3. additiondiluted with water (13 mL)
4. extractionthen extracted with EA (30 mL)
5. dry with materialThe organic layer was dried over Na2SO4
6. concentrationconcentrated to a residue which
7. customwas purified by Prep TLC
8. washeluted with PE/EA (2:1)