Potassium Carbonate → 1-[1-(4-Fluorophenyl)-5-isopropylpyrazol-4-yl]-3-[4-(trifluoromethyl)imidazol-1-yl]pyrrolidin-2-one

HRID 522323Notes

Reaction equation

HRID 522323 reaction equation
Br[CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[N:9][N:10]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[C:11]=2[CH:12]([CH3:14])[CH3:13])[C:3]1=[O:22].[F:23][C:24]([F:31])([F:30])[C:25]1[N:26]=[CH:27][NH:28][CH:29]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[F:21][C:18]1[CH:19]=[CH:20][C:15]([N:10]2[C:11]([CH:12]([CH3:14])[CH3:13])=[C:7]([N:4]3[CH2:5][CH2:6][CH:2]([N:28]4[CH:29]=[C:25]([C:24]([F:31])([F:30])[F:23])[N:26]=[CH:27]4)[C:3]3=[O:22])[CH:8]=[N:9]2)=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 867230343-Bromo-1-[1-(4-fluorophenyl)-5-isopropylpyrazol-4-yl]pyrrolidin-2-oneHCID 178418921HCID 178418921, compound

Product 1

HCID 747665871-[1-(4-Fluorophenyl)-5-isopropylpyrazol-4-yl]-3-[4-(trifluoromethyl)imidazol-1-yl]pyrrolidin-2-oneYield 94.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 3-bromo-1-[1-(4-fluorophenyl)-5-isopropyl-pyrazol-4-yl]pyrrolidin-2-one (0.020 g, 0.055 mmol), 4-(trifluoromethyl)-1H-imidazole (0.024 g, 0.17 mmol) and K2CO3 (0.030 g, 0.22 mmol) in DMF (0.6 mL) was stirred at 60° C. for 1 hr. The mixture was then cooled to room temperature, quenched with water (30 mL) and extracted with EtOAc (50 mL). The organic layer was separated, dried over anhydrous sodium sulfate, concentrated in vacuo and purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to yield the title compound (0.022 g, TFA salt, 75%); 1H NMR (TFA salt) (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.59 (s, 1H), 7.51 (s, 1H), 7.39 (dd, J=8.4, 4.8 Hz, 2H), 7.20 (dd, J=8.6, 8.6 Hz, 2H), 5.06 (dd, J=10.8, 8.8 Hz, 1H), 3.90 (m, 1H), 3.83 (m, 1H), 2.98 (m, 2H), 2.54 (m, 1H), 1.21 (d, J=7.2 Hz, 3H), 1.20 (d, J=7.2 Hz, 3H); MS: (ES) m/z calculated for C20H19F4N5O (free form) [M+H]+ 422.1. found 422.1.

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. customquenched with water (30 mL)
  3. extractionextracted with EtOAc (50 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. custompurified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-0c46512a0bfe4baf9337ce0ce2e8ee95
Source dataset
uspto-grants-2016_05
Patent number
US09328116B2

Reaction notes

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