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

HRID 60466Notes

Reaction equation

HRID 60466 reaction equation
[CH:1]([C:4]1[CH:5]=[C:6]([CH:31]=[CH:32][CH:33]=1)[O:7][C:8]1[CH:30]=[N:29][C:11]2[N:12]([CH3:28])[C:13](=[O:27])[N:14]([CH2:17][CH2:18][CH2:19][O:20][CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][O:22]3)[C:15](=[O:16])[C:10]=2[CH:9]=1)([CH3:3])[CH3:2].[Li+].CC([N-]C(C)C)C.[CH:42](=[O:49])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>C1COCC1>[OH:49][CH:42]([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:9]1[C:10]2[C:15](=[O:16])[N:14]([CH2:17][CH2:18][CH2:19][O:20][CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][O:22]3)[C:13](=[O:27])[N:12]([CH3:28])[C:11]=2[N:29]=[CH:30][C:8]=1[O:7][C:6]1[CH:31]=[CH:32][CH:33]=[C:4]([CH:1]([CH3:3])[CH3:2])[CH:5]=1

Participants

5

Reactant 3

HCID 240BenzaldehydeHCID 2724682Lithium diisopropylamideHCID 1188755256-(3-isopropylphenoxy)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1188754805-(hydroxy(phenyl)methyl)-6-(3-isopropylphenoxy)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 6-(3-isopropylphenoxy)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (220 mg, 0.50 mmol) in THF (10 mL) at −78° C. was added LDA (2.0 M in THF, 1.25 mL, 2.50 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then a solution of benzaldehyde (106 mg, 1.00 mmol) in THF (2 mL) was added dropwise. The reaction was stirred at −78° C. for 1 h, quenched with aq. NH4Cl (10 mL) then diluted with EA (20 mL) and water (20 mL). The organic layer was dried over Na2SO4 and concentrated to give a residue which was purified by chromatography PE/EA (7:1) to give 5-(hydroxy(phenyl)methyl)-6-(3-isopropylphenoxy)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (120 mg, 45% yield) as a solid. LCMS: MH+ 560 and TR=1.869 min.

Workup

  1. stirringThe reaction was stirred at −78° C. for 1 h
  2. customquenched with aq. NH4Cl (10 mL)
  3. additionthen diluted with EA (20 mL) and water (20 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customto give a residue which
  7. customwas purified by chromatography PE/EA (7:1)

Sources & evidence

ORD record
ord-84c7afcf87e5424e88a5d801b97d25ef
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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