Ethyl Bromide → HCID 57422495, compound

HRID 548184Notes

Reaction equation

HRID 548184 reaction equation
[CH2:1]([N:8]1[C:12](=[O:13])[N:11]([C:14]2[CH:15]=[N:16][N:17]([CH2:19][C:20]3[C:21]([CH3:26])=[N:22][O:23][C:24]=3[CH3:25])[CH:18]=2)[C:10](=[O:27])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:29][CH3:30].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.[Cl-].[Na+].O>[CH2:1]([N:8]1[C:12](=[O:13])[N:11]([C:14]2[CH:15]=[N:16][N:17]([CH2:19][C:20]3[C:21]([CH3:26])=[N:22][O:23][C:24]=3[CH3:25])[CH:18]=2)[C:10](=[O:27])[N:9]1[CH2:29][CH3:30])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 6332Ethyl BromideHCID 10796Cesium carbonateHCID 57422493HCID 57422493, compound

Product 1

HCID 57422495HCID 57422495, compoundYield 37.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

1-benzyl-4-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1,2,4-triazolidine-3,5-dione (100 mg, 0.27 mmol), bromoethane (149 mg, 1.36 mmol), and cesium carbonate (355 mg, 1.1 mmol) in DMF (5 mL) were heated at 80° C. for 15 hours. The reaction was cooled to room temperature, diluted with brine (50 mL) and extracted with ethyl acetate (2×, 50 mL). The combined organic extracts were dried over magnesium sulfate, filtered and concentrated on the rotovap. The residue was purified by HPLC (5 to 95% acetonitrile in H2O: 25 minute gradient) to afford 1-benzyl-4-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2-ethyl-1,2,4-triazolidine-3,5-dione (40 mg, 37%) as an oil. 1H NMR (DMSO-d6, 400 MHz): δ0.97 (t, J=7.2 Hz, 3H), 2.13 (s, 3H), 2.39 (s, 3H), 3.58 (q, J=6.8 Hz, 2H), 4.80 (s, 2H), 5.18 (s, 2H), 7.28-7.36 (m, 5H), 7.77 (s, 1H), 8.19 (s, 1H). MS M+H calculated 395.18; found 395.2. The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 0.04 μM.

Workup

  1. extractionextracted with ethyl acetate (2×, 50 mL)
  2. dry with materialThe combined organic extracts were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated on the rotovap
  5. customThe residue was purified by HPLC (5 to 95% acetonitrile in H2O: 25 minute gradient)

Sources & evidence

ORD record
ord-2670143b5fae45aba6488a600c7627fc
Source dataset
uspto-grants-2011_05
Patent number
US07939671B2

Reaction notes

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