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

HRID 522333Notes

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]([Cl:21])=[CH:17][CH:16]=3)[C:11]=2[CH:12]([CH3:14])[CH3:13])[C:3]1=[O:22].[CH2:23]([C:25]1[NH:26][CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[N:29]=1)[CH3:24].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl: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:26]4[CH:27]=[C:28]([C:30]([F:31])([F:32])[F:33])[N:29]=[C:25]4[CH2:23][CH3:24])[C:3]3=[O:22])[CH:8]=[N:9]2)=[CH:16][CH:17]=1

Participants

Conditions

Temperature: 65 °C

Procedure

A mixture of 3-bromo-1-[1-(4-chlorophenyl)-5-isopropylpyrazol-4-yl]pyrrolidin-2-one (0.200 g, 0.52 mmol), 2-ethyl-4-(trifluoromethyl)-1H-imidazole (0.060 g, 0.36 mmol) and K2CO3 (0.080 g, 0.58 mmol) in DMF (1.5 mL) was stirred at 65° C. for 1.5 hrs. The mixture was then cooled to room temperature, quenched with water (30 mL), extracted with EtOAc (50 mL), and purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to yield the title compound (0.0022 g, TFA salt, 1.0%). 1H NMR (TFA salt) (400 MHz, CDCl3) δ 7.58 (s, 1H), 7.49 (m, 2H), 7.35 (m, 2H), 7.21 (s, 1H), 5.03 (dd, J=10.4, 8.8 Hz, 1H), 3.88 (m, 1H), 3.81 (m, 1H), 3.03 (heptet, J=7.0 Hz, 1H), 2.88 (m, 2H), 2.30 (m, 2H), 1.40 (t, J=7.4 Hz, 3H), 1.23 (m, 6H); MS: (ES) m/z calculated for C22H23ClF3N5O [M+H]+ 466.1. found 466.1.

Workup

temperatureThe mixture was then cooled to room temperature
customquenched with water (30 mL)
extractionextracted with EtOAc (50 mL)
custompurified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record: ord-0fc5a1bf83bf47a9aa6aa392818a5478
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328116B2

Reaction notes

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