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

HRID 60169Notes

Reaction equation

HRID 60169 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]([O:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=3)[N:21]=[CH:22][C:15]=2[N:14]([CH3:31])[C:13]1=[O:32])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li+].CC([N-]C(C)C)C.[Cl:41][C:42]1[CH:49]=[CH:48][C:45]([CH:46]=[O:47])=[CH:44][CH:43]=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:46]([C:45]3[CH:48]=[CH:49][C:42]([Cl:41])=[CH:43][CH:44]=3)[OH:47])=[C:20]([O:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=3)[N:21]=[CH:22][C:15]=2[N:14]([CH3:31])[C:13]1=[O:32])([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 77264-ChlorobenzaldehydeHCID 2724682Lithium diisopropylamideHCID 1317370843-(3-(tert-butyldimethylsilyloxy)propyl)-6-(3-chlorophenoxy)-1-methyl pyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1317370853-(3-(tert-butyldimethylsilyloxy)propyl)-6-(3-chlorophenoxy)-5-((4-chlorophenyl)(hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dioneYield 29%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-(3-chlorophenoxy)-1-methyl pyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (150 mg, 0.315 mmol) in THF (4 mL) at −78° C. was added LDA (2.0 M in THF, 0.79 mL, 1.58 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then a solution of 4-chlorobenzaldehyde (88 mg, 0.625 mmol) in THF (1 mL) was added. The reaction was stirred at −78° C. for 30 min, quenched with aq. NH4Cl (3 mL) then diluted EA (20 mL) and water (20 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography PE/EA (2:1) to give 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-(3-chlorophenoxy)-5-((4-chlorophenyl)(hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (56 mg, 29% yield) as a solid. LCMS: (M+-OH) 598 and TR=2.221 min.

Workup

  1. stirringThe reaction was stirred at −78° C. for 30 min
  2. customquenched with aq. NH4Cl (3 mL)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated to a residue which
  5. customwas purified by chromatography PE/EA (2:1)

Sources & evidence

ORD record
ord-66a6e1d2acff44beb963328a05423832
Source dataset
uspto-grants-2016_09
Patent number
US09440973B2

Reaction notes

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