Reaktion #88709

Reaktionsgleichung

4-chlorobenzaldehyde

1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-((5-(trifluoromethyl)pyridin-3-yl)oxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

LDA

→

5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-((5-(trifluoromethyl)pyridin-3-yl)oxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Ausbeute 39.1%

Lösungsmittel

EA

water

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe reaction was stirred for 30 min at −78° C.
2. 2
   TrocknenThe organic layer was dried over Na2SO4
3. 3
   Einengenconcentrated to a residue which
4. 4
   Sonstigewas purified by chromatography
5. 5
   Wascheneluted with PE/EA (10:1 to 1:1)

Vorschrift

To a solution of 1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-((5-(trifluoromethyl)pyridin-3-yl)oxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (340 mg, 0.708 mmol) in THF (8 mL) at −78° C. was added LDA (2M in THF, 1.42 mL, 2.83 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then a solution of 4-chlorobenzaldehyde (199.7 mg, 1.42 mmol) in THF (2 mL) was added dropwise. 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-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-((5-(trifluoromethyl)pyridin-3-yl)oxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (172 mg, 39.1% yield) as an oil. LCMS: [MH+-THP] 537 and TR=1.611 min.

Quelle