Benzyl Bromide → 1-benzyl-4-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2-methyl-1,2,4-triazolidine-3,5-dione

HRID 2095007Notes

Reaction equation

HRID 2095007 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])[N:16]([CH3:19])[NH:15][C:14]3=[O:20])[CH:10]=[N:9]2)=[C:5]([CH3:21])[O:4][N:3]=1.C(N(CC)CC)C.[CH2:29](Br)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>C(#N)C>[CH2:29]([N:15]1[C:14](=[O:20])[N:13]([C:11]2[CH:10]=[N:9][N:8]([CH2:7][C:6]3[C:2]([CH3:1])=[N:3][O:4][C:5]=3[CH3:21])[CH:12]=2)[C:17](=[O:18])[N:16]1[CH3:19])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 8471TriethylamineHCID 57422478HCID 57422478, compound

Product 1

HCID 574224821-benzyl-4-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2-methyl-1,2,4-triazolidine-3,5-dioneYield 20.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1-methyl-1,2,4-triazolidine-3,5-dione (example 10-64) (785 mg, 2.7 mmol) was dissolved in acetonitrile (50 mL). Triethylamine (1 g, 10 mmol) and benzyl bromide (510 mg, 3 mmol) were added and the reaction was stirred at ambient temperature for 12 hours. The mixture was then concentrated on the rotovap, dissolved in methanol (5 mL) and purified by reversed phase HPLC (5-95% acetonitrile in H2O: 25 minute gradient). The pure fractions were pooled and concentrated and the product was recrystallized form ethanol to afford 1-benzyl-4-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2-methyl-1,2,4-triazolidine-3,5-dione (210 mg, 20%) as a white solid. 1H NMR (DMSO-d6, 400 MHz): δ2.13 (s, 3H), 2.39 (s, 3H), 3.09 (s, 3H), 4.81 (s, 2H), 5.18 (s, 2H), 7.30-7.35 (m, 5H), 7.76 (s, 1H), 8.18 (s, 1H). MS M+H calculated 381.1; found 381.1. Melting point: 124-126° C. The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 0.02 μM.

Workup

  1. concentrationThe mixture was then concentrated on the rotovap
  2. dissolutiondissolved in methanol (5 mL)
  3. custompurified by reversed phase HPLC (5-95% acetonitrile in H2O: 25 minute gradient)
  4. concentrationconcentrated
  5. customthe product was recrystallized form ethanol

Sources & evidence

ORD record
ord-70e68765aa4f43d9a473aad476f657b1
Source dataset
uspto-grants-2013_05
Patent number
US08445692B2

Reaction notes

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