Dimethylformamide → 3-[3-(Azetidin-3-ylamino)-4-(trifluoromethoxy)phenyl]-5,5-dimethyl-1-(pyridin-4-ylmethyl)imidazolidine-2,4-dione;2,2,2-trifluoroacetic acid

HRID 2356954Notes

Reaction equation

HRID 2356954 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([N:13]2[C:17](=[O:18])[C:16]([CH3:20])([CH3:19])[N:15]([CH2:21][C:22]3[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=3)[C:14]2=[O:28])[CH:5]=[CH:6][C:7]=1[O:8][C:9]([F:12])([F:11])[F:10].[C:29](=O)([O-:31])[O-:30].[K+].[K+].[CH:35]([O-])=O.[NH4+].[CH3:39][N:40]([CH:42]=O)C>CO.[Pd]>[F:12][C:9]([F:10])([F:11])[C:29]([OH:31])=[O:30].[NH:40]1[CH2:42][CH:35]([NH:1][C:2]2[CH:3]=[C:4]([N:13]3[C:17](=[O:18])[C:16]([CH3:20])([CH3:19])[N:15]([CH2:21][C:22]4[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=4)[C:14]3=[O:28])[CH:5]=[CH:6][C:7]=2[O:8][C:9]([F:10])([F:11])[F:12])[CH2:39]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 2723923Ammonium formateHCID 231103083-(3-Amino-4-trifluoromethoxyphenyl)5,5-dimethyl-1-pyridin-4-ylmethylimidazolidine-2,4-dione

Product 1

HCID 866172253-[3-(Azetidin-3-ylamino)-4-(trifluoromethoxy)phenyl]-5,5-dimethyl-1-(pyridin-4-ylmethyl)imidazolidine-2,4-dione;2,2,2-trifluoroacetic acid

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

394 mg (1 mmol) of 3-(3-amino-4-trifluoromethoxyphenyl)-5,5-dimethyl-1-pyridin-4-ylmethylimidazolidine-2,4-dione were dissolved in 1 ml of DMF, 166 mg (1.2 mmol) of potassium carbonate and 413 mg (1.3 mmol) of 1-(diphenylmethyl)-3-azetidine methanesulphonate were added, and the mixture was stirred at 80° C. for 5 h. For workup, the mixture was added to ice-water, extracted with CH2C12, dried and concentrated. The remaining residue was purified by means of preparative HPLC (RP18, acetonitrile/water, 0.1% TFA). The intermediate obtained in this way was dissolved in 3 ml of methanol, admixed with 10 mg of 5% Pd/C and 50 mg (0.8 mmol) of ammonium formate, and heated under reflux for 2 h. The residue remaining after filtration and evaporation was purified by means of preparative HPLC (RP18, acetonitrile/water, 0.1% TFA).

Workup

  1. extractionextracted with CH2C12
  2. customdried
  3. concentrationconcentrated
  4. customThe remaining residue was purified by means of preparative HPLC (RP18, acetonitrile/water, 0.1% TFA)
  5. customThe intermediate obtained in this way
  6. temperatureheated
  7. temperatureunder reflux for 2 h
  8. filtrationafter filtration and evaporation
  9. customwas purified by means of preparative HPLC (RP18, acetonitrile/water, 0.1% TFA)

Sources & evidence

ORD record
ord-a43a9470e0844dce9252d0a8ad53c660
Source dataset
uspto-grants-2010_07
Patent number
US07759379B2

Reaction notes

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