4-Chlorobenzaldehyde → 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-((4-chlorophenyl) (hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

HRID 60162Notes

Reaction equation

HRID 60162 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:17](=[O:18])[C:16]2[CH:19]=[C:20]([Cl:23])[N:21]=[CH:22][C:15]=2[N:14]([CH3:24])[C:13]1=[O:25])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li+].CC([N-]C(C)C)C.[Cl:34][C:35]1[CH:42]=[CH:41][C:38]([CH:39]=[O:40])=[CH:37][CH:36]=1>C1COCC1>[Si:1]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:17](=[O:18])[C:16]2[C:19]([CH:39]([C:38]3[CH:41]=[CH:42][C:35]([Cl:34])=[CH:36][CH:37]=3)[OH:40])=[C:20]([Cl:23])[N:21]=[CH:22][C:15]=2[N:14]([CH3:24])[C:13]1=[O:25])([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 77264-ChlorobenzaldehydeHCID 2724682Lithium diisopropylamideHCID 1317370803-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-1-methyl pyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1317370763-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-((4-chlorophenyl) (hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dioneYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (383 mg, 1 mmol) in THF (4 mL) at −78° C. was added LDA (1.8N in THF, 2.7 mL, 4.86 mmol) dropwise. The reaction was stirred at −78° C. for 30 min then 4-chlorobenzaldehyde (280 mg, 2 mmol) in THF (1 mL) was added dropwise. After stirring for 20 min the reaction was quenched with aq. NH4Cl (2 mL) then diluted with EA (5 mL) and water (2 mL). The organic layer was washed with brine (5 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (2:1) to give 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-((4-chlorophenyl)(hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (155 mg, 30% yield) as a white solid. LCMS: (M+-OH—H) 506 and TR=2.357 min.

Workup

  1. stirringAfter stirring for 20 min the reaction
  2. customwas quenched with aq. NH4Cl (2 mL)
  3. additionthen diluted with EA (5 mL) and water (2 mL)
  4. washThe organic layer was washed with brine (5 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to a residue which
  7. customwas purified by chromatography
  8. washeluted with PE/EA (2:1)

Sources & evidence

ORD record
ord-b4994c53334043efabb9332e8564e7bb
Source dataset
uspto-grants-2016_09
Patent number
US09440973B2

Reaction notes

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