Dimethylamine → HCID 57944908, compound

HRID 658705Notes

Reaction equation

HRID 658705 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][NH:15][C:14]3=[O:19])[CH:10]=[N:9]2)=[C:5]([CH3:20])[O:4][N:3]=1.BrCC1C=CC=C(CBr)C=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:38][C:39]1[CH:40]=[C:41]([CH:63]=[CH:64][CH:65]=1)[CH2:42][N:43]1[CH2:47]C(=O)N(C2C=NN(CC3C(C)=NOC=3C)C=2)[C:44]1=O.CNC.[H-].[Na+]>CN(C=O)C.C1COCC1.C(O)C>[CH3:44][N:43]([CH2:42][C:41]1[CH:40]=[C:39]([CH:65]=[CH:64][CH:63]=1)[CH2:38][N:15]1[CH2:16][C:17](=[O:18])[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[CH3:20])[CH:12]=2)[C:14]1=[O:19])[CH3:47]

Participants

10

Reactant 6

HCID 674DimethylamineHCID 10796Cesium carbonateHCID 24758Sodium hydrideHCID 69373Benzene, 1,3-bis(bromomethyl)-HCID 574224243-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)imidazolidine-2,4-dioneHCID 60208916HCID 60208916, compound

Product 1

HCID 57944908HCID 57944908, compoundYield 13%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)imidazolidine-2,4-dione (example 10-1) (275 mg, 1 mmol) 1,3-bis(bromomethyl)benzene (263 mg, 1 mmol), and cesium carbonate (325 mg, 1 mmol) were dissolved in 2 mL DMF and irradiated in the microwave reactor at 165° C. for 5 minutes. The reaction was cooled to room temperature, and salt precipitate was removed by filtration. The clear solution containing crude product was concentrated and redissolved in ethyl acetate. The organic solution was washed with water twice followed by brine. The organic layer was dried over sodium sulfate and evaporated to give the crude product which was carried forward to the next step without further purification or characterization. 1-(3-(bromomethyl)benzyl)-3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)imidazolidine-2,4-dione (example 42a) (152 mg, 0.3 mmol), dimethylamine (2 M solution in THF) (1.5 mL, 3 mmol), and sodium hydride (9 mg, 0.36 mmol) were dissolved in 1 mL anhydrous THF. The reaction was placed in a microwave reactor for 5 minutes at 120° C. The crude product was redissolved in 2 mL ethanol and was purified by HPLC (10-95% Acetonitrile/Water, 25 minutes) to afford 1-(3-((dimethylamino)methyl)benzyl)-3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)imidazolidine-2,4-dione(16 mg, 13%). MS M+H calculated 423.1; found 423.1. The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 1.2 uM.

Workup

  1. customirradiated in the microwave reactor at 165° C. for 5 minutes
  2. customsalt precipitate was removed by filtration
  3. additionThe clear solution containing crude product
  4. concentrationwas concentrated
  5. dissolutionredissolved in ethyl acetate
  6. washThe organic solution was washed with water
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. customevaporated
  9. customto give the crude product which
  10. customwas carried forward to the next step without further purification or characterization
  11. customwas purified by HPLC (10-95% Acetonitrile/Water, 25 minutes)

Sources & evidence

ORD record
ord-27cc57d5fd274de892e1d2bc7212cc56
Source dataset
uspto-grants-2011_12
Patent number
US08076491B2

Reaction notes

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