反应详情

温度

-78 °C

To a solution of 1-methyl-6-(5-methylpyridin-3-yloxy)-3-(3-(tetrahydro-2H-pyran-2-yloxy) propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 27, step 1, 140 mg, 0.330 mmol) in THF (10 mL) at −78° C. was added LDA (2M in THF, 0.84 mL, 1.65 mmol) dropwise The reaction was stirred at −78° C. for 1 h then a solution of 6-(trifluoromethyl) nicotinaldehyde (115 mg, 0.660 mmol) in THF (2 mL) was added. The reaction was stirred for 30 min at −78° C. then diluted with EA (10 mL) and water (10 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (10:1 to 1:1) to give 5-(hydroxy(6-(trifluoromethyl)pyridin-3-yl)methyl)-1-methyl-6-(5-methylpyridin-3-yloxy)-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4 (1H,3H)-dione (24 mg, 12.1% yield) as a yellow oil. LCMS: [MH+-THP] 518 and TR=1.494 min.

1. stirringThe reaction was stirred for 30 min at −78° C.
2. dry with materialThe organic layer was dried over Na2SO4
3. concentrationconcentrated to a residue which
4. customwas purified by chromatography
5. washeluted with PE/EA (10:1 to 1:1)