Benzaldehyde → 5-(hydroxy(phenyl)methyl)-6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60469Notes

Reaction equation

HRID 60469 reaction equation
[CH:1]([O:4][C:5]1[CH:27]=[N:26][C:8]2[N:9]([CH3:25])[C:10](=[O:24])[N:11]([CH2:14][CH2:15][CH2:16][O:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)[C:12](=[O:13])[C:7]=2[CH:6]=1)([CH3:3])[CH3:2].[Li+].CC([N-]C(C)C)C.[CH:36](=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C1COCC1>[OH:43][CH:36]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:6]1[C:7]2[C:12](=[O:13])[N:11]([CH2:14][CH2:15][CH2:16][O:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)[C:10](=[O:24])[N:9]([CH3:25])[C:8]=2[N:26]=[CH:27][C:5]=1[O:4][CH:1]([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 240BenzaldehydeHCID 2724682Lithium diisopropylamideHCID 1188754856-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione2×

Product 1

HCID 1188754835-(hydroxy(phenyl)methyl)-6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 51.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 36, step 3, 150 mg, 0.4 mmol) in THF (6 mL) at −78° C. was added LDA (2M in THF, 1.0 mL, 2 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then benzaldehyde (84.8 mg, 0.8 mmol) in THF (1.5 mL) was added. The reaction was stirred at −78° C. for 1 h quenched with aq. NH4Cl (8 mL) then diluted with EA (30 mL) and water (10 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by Prep TLC eluted with PE/EA (2:1) to give 5-(hydroxy(phenyl)methyl)-6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (100 mg, 51.8% yield) as a solid. LCMS: [M+-THP-OH] 382 and TR=1.855 min.

Workup

  1. stirringThe reaction was stirred at −78° C. for 1 h
  2. customquenched with aq. NH4Cl (8 mL)
  3. additionthen diluted with EA (30 mL) and water (10 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated to a residue which
  6. customwas purified by Prep TLC
  7. washeluted with PE/EA (2:1)

Sources & evidence

ORD record
ord-b039a36ee1c04c3d93d13437d368b76e
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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