Methyl iodide → HCID 57422485, compound

HRID 658729Notes

Reaction equation

HRID 658729 reaction equation
[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[CH:12]=[C:11]([N:13]3[C:17](=O)[NH:16][NH:15][C:14]3=[O:19])[CH:10]=[N:9]2)=[C:5]([CH3:20])[O:4][N:3]=1.CI.[C:23](=[O:26])([O-])[O-].[Cs+].[Cs+].[C:29](#N)C.CN(C=O)C>Cl>[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[CH:12]=[C:11]([N:13]3[C:14](=[O:19])[N:15]([CH3:29])[N:16]([CH3:17])[C:23]3=[O:26])[CH:10]=[N:9]2)=[C:5]([CH3:20])[O:4][N:3]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 21891449acetonitrile N,N-dimethylformamideHCID 57422484HCID 57422484, compound

Product 1

HCID 57422485HCID 57422485, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

4-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1,2,4-triazolidine-3,5-dione (example 10-68) (100 mg, 0.36 mmol), methyl iodide (141 mg, 1 mmol), and cesium carbonate (325 mg, 1 mmol) were stirred in a 2/1 mixture of acetonitrile/DMF (5 mL) at ambient temperature for 2 hours. The mixture was diluted with aqueous 1N HCl (100 mL) and extracted with ethyl acetate (3×, 50 mL). The combined organic extracts were dried over sodium sulfate, concentrated and the crude residue taken up in MeOH and purified by reversed phase HPLC (5 to 95% acetonitrile in H2O: 25 minute gradient). The pure fractions were pooled and concentrated to afford 4-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1,2-dimethyl-1,2,4-triazolidine-3,5-dione (89 mg, 80%) as a clear semi-solid. NMR (CDCl3, 400 MHz): δ2.18 (s, 3H), 2.41 (s, 3H), 3.22 (s, 6H), 5.04 (s, 2H), 7.88 (s, 1H), 8.03 (s, 1H). The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 0.6 μM.

Workup

  1. extractionextracted with ethyl acetate (3×, 50 mL)
  2. dry with materialThe combined organic extracts were dried over sodium sulfate
  3. concentrationconcentrated
  4. custompurified by reversed phase HPLC (5 to 95% acetonitrile in H2O: 25 minute gradient)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-5d3decf1f35447169a739fcb94875931
Source dataset
uspto-grants-2011_12
Patent number
US08076491B2

Reaction notes

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