Benzyl Bromide → HCID 57422491, compound

HRID 548179Notes

Reaction equation

HRID 548179 reaction equation
[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[CH:12]=[C:11]([N:13]3[CH2:17][CH2:16][NH:15][C:14]3=[O:18])[CH:10]=[N:9]2)=[C:5]([CH3:19])[O:4][N:3]=1.[H-].[Na+].[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>CN(C=O)C>[CH2:22]([N:15]1[CH2:16][CH2:17][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[CH3:19])[CH:12]=2)[C:14]1=[O:18])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 57422490HCID 57422490, compound

Product 1

HCID 57422491HCID 57422491, compoundYield 31.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

1-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)imidazolidin-2-one (example 10-88a) (50 mg, 0.19 mmol) and 60% sodium hydride (8 mg, 0.21 mmol) in DMF (3 mL) were stirred at room temperature for 15 minutes then cooled to 0° C. Benzyl bromide (33 mg, 0.19 mmol) was added to the mixture and allowed to warm up at room temperature for 2 hours. The reaction was quenched with methanol and concentrated on the rotovap. The reaction was diluted with brine (50 mL) and extracted with dichloromethane (2×, 50 mL). The combined organic extracts were dried over magnesium sulfate, filtered and concentrated on the rotovap. The residue was purified by silica column chromotography (100% to 90% dichloromethane in methanol: 30 minute gradient) to afford 1-benzyl-3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)imidazolidin-2-one (21 mg, 31%) as a white solid. MS M+H calculated 352.17; found 352.2. The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 0.71 μM.

Workup

  1. temperatureto warm up at room temperature for 2 hours
  2. customThe reaction was quenched with methanol
  3. concentrationconcentrated on the rotovap
  4. additionThe reaction was diluted with brine (50 mL)
  5. extractionextracted with dichloromethane (2×, 50 mL)
  6. dry with materialThe combined organic extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated on the rotovap
  9. customThe residue was purified by silica column chromotography (100% to 90% dichloromethane in methanol: 30 minute gradient)

Sources & evidence

ORD record
ord-bb981fb231bf455d8a85ce1dd2549fed
Source dataset
uspto-grants-2011_05
Patent number
US07939671B2

Reaction notes

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