반응 #88722

반응 방정식

4-chlorobenzaldehyde

6-bromo-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

LDA

→

6-bromo-5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

수율 18.5%

용매

THF

THF

반응 조건

후처리

1. 1
   workup.STIRRINGThe reaction was stirred at −78° C. for 1 h
2. 2
   기타quenched with aq. NaHCO3 (5 mL)
3. 3
   workup.ADDITIONthen diluted with EA (50 mL) and water (20 mL)
4. 4
   건조The organic layer was dried over Na2SO4
5. 5
   농축concentrated to a residue which
6. 6
   기타was purified by chromatography PE/EA (4:1)

실험 절차

To a solution of 6-bromo-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (0.6 g, 1.51 mmol) in THF (10 mL) at −78° C. was added LDA (1.8 M in THF, 4.2 mL, 7.56 mmol) dropwise. The reaction was stirred at −78° C. for 30 min then a solution of 4-chlorobenzaldehyde (0.42 g, 3 mmol) in THF (2 mL) was added. The reaction was stirred at −78° C. for 1 h, quenched with aq. NaHCO3 (5 mL) then diluted with EA (50 mL) and water (20 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography PE/EA (4:1) to give 6-bromo-5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (150 mg, 18.5% yield) as a white solid. LCMS: [M+-THP] 436 and TR=1.900 min.

출처