Methyl iodide → 1-[1-(4-Chlorophenyl)-5-isopropyl-pyrazol-4-yl]-3-methyl-3-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]pyrrolidin-2-one

HRID 522313Notes

Reaction equation

HRID 522313 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH:13]([CH3:15])[CH3:14])=[C:11]([N:16]3[CH2:20][CH2:19][CH:18]([N:21]4[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[N:23]=[C:22]4[CH3:30])[C:17]3=[O:31])[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[H-].[Na+].CI.[NH4+].[Cl-].[C:38](O)(C(F)(F)F)=O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([CH:13]([CH3:14])[CH3:15])=[C:11]([N:16]3[CH2:20][CH2:19][C:18]([CH3:38])([N:21]4[CH:25]=[C:24]([C:26]([F:28])([F:27])[F:29])[N:23]=[C:22]4[CH3:30])[C:17]3=[O:31])[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 6328Methyl iodideHCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 762829761-[1-(4-Chlorophenyl)-5-isopropylpyrazol-4-yl]-3-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]pyrrolidin-2-one

Product 1

HCID 762827291-[1-(4-Chlorophenyl)-5-isopropyl-pyrazol-4-yl]-3-methyl-3-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]pyrrolidin-2-oneYield 27%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-[1-(4-chlorophenyl)-5-isopropylpyrazol-4-yl]-3-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]pyrrolidin-2-one (50 mg, 0.11 mmol) was added DMF (2 mL) and NaH (60% in mineral oil, 16 mg, 0.33 mmol) slowly at room temperature under nitrogen atmosphere. After stirring for 10 min at room temperature, MeI (34 μL, 0.55 mmol) was added and further stirred for 2 h. Saturated NH4Cl solution (10 mL) was then added at 0° C. slowly to the reaction mixture followed by extraction with EtOAc (2×25 mL). The combined EtOAc layers were dried (MgSO4), concentrated in vacuo, and purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give 1-[1-(4-chlorophenyl)-5-isopropyl-pyrazol-4-yl]-3-methyl-3-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]pyrrolidin-2-one (17 mg, 0.029 mmol, 27% yield) as a TFA salt. 1H NMR (400 MHz, Methanol-d4) δ 7.88 (s, 1H), 7.70 (s, 1H), 7.59 (d, J=11.76 Hz, 2H), 7.42 (d, J=11.76 Hz, 2H), 3.86-3.95 (m, 2H), 2.99-3.08 (m, 1H), 2.58-2.80 (m, 2H), 2.52 (s, 3H), 1.96 (s, 3H), 1.22 (d, J=23.4 Hz, 3H), 1.20 (d, J=23.4 Hz, 3H); MS: (ES) m/z calculated for C22H23ClF3N5O [M+H]+466.9. found 466.1.

Workup

  1. stirringfurther stirred for 2 h
  2. extractionfollowed by extraction with EtOAc (2×25 mL)
  3. dry with materialThe combined EtOAc layers were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. custompurified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-53ffc3a9417d4d36a340a50292a43097
Source dataset
uspto-grants-2016_05
Patent number
US09328116B2

Reaction notes

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