3-((3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2,4-dioxoimidazolidin-1-yl)methyl)benzaldehyde → 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1-(3-(hydroxymethyl)benzyl)imidazolidine-2,4-dione

HRID 548134Notes

Reaction equation

HRID 548134 reaction equation
[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[CH:12]=[C:11]([N:13]3[C:17](=[O:18])[CH2:16][N:15]([CH2:19][C:20]4[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=4)[CH:23]=[O:24])[C:14]3=[O:28])[CH:10]=[N:9]2)=[C:5]([CH3:29])[O:4][N:3]=1>C(O)C.[Pd]>[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[CH:12]=[C:11]([N:13]3[C:17](=[O:18])[CH2:16][N:15]([CH2:19][C:20]4[CH:27]=[CH:26][CH:25]=[C:22]([CH2:23][OH:24])[CH:21]=4)[C:14]3=[O:28])[CH:10]=[N:9]2)=[C:5]([CH3:29])[O:4][N:3]=1

Participants

4

Reactant 1

HCID 574224463-((3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2,4-dioxoimidazolidin-1-yl)methyl)benzaldehyde

Product 1

HCID 574224543-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1-(3-(hydroxymethyl)benzyl)imidazolidine-2,4-dione

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

3-((3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2,4-dioxoimidazolidin-1-yl)methyl)benzaldehyde (example 10-24) (131 mg, 0.3 mmol) was dissolved in 2 mL ethanol. The solution was passed through the H-Cube instrument at room temperature using 10% Pd/C catalyst at a flow rate of 1 ml/minute. The collected fraction was concentrated, redissolved in 2 mL ethanol and purified by HPLC (10-95% Acetonitrile/Water, 25 minutes). The purified fractions were combined and concentrated to give the title compound. 1H NMR (DMSO, 400 MHz): δ2.123 (s, 3H), 2.388 (s, 3H), 3.978 (s, 2H), 4.516 (s, 2H), 5.182 (s, 2H), 7.242 (m, 4H), 7.779 (s, 1H), 8.172 (s, 1H), 8.505 (s, 1H). MS M+H calculated 396.1; found 396.1. The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 0.3 uM. Yield: 24 mg, 18%.

Workup

  1. customwas passed through the H-Cube instrument at room temperature
  2. concentrationThe collected fraction was concentrated
  3. dissolutionredissolved in 2 mL ethanol
  4. custompurified by HPLC (10-95% Acetonitrile/Water, 25 minutes)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-713c2bbc33c749db8d984f8e0f18bfa5
Source dataset
uspto-grants-2011_05
Patent number
US07939671B2

Reaction notes

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