Potassium Carbonate → 3-[4-Chloro-5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-1-[1-(4-chlorophenyl)-5-isopropylpyrazol-4-yl]pyrrolidin-2-one

HRID 522331Notes

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].[Cl:23][C:24]1[C:25]([CH3:33])=[N:26][NH:27][C:28]=1[C:29]([F:32])([F:31])[F:30].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:23][C:24]1[C:28]([C:29]([F:31])([F:30])[F:32])=[N:27][N:26]([CH:2]2[CH2:6][CH2:5][N:4]([C:7]3[CH:8]=[N:9][N:10]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=4)[C:11]=3[CH:12]([CH3:14])[CH3:13])[C:3]2=[O:22])[C:25]=1[CH3:33]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 3-bromo-1-[1-(4-chlorophenyl)-5-isopropylpyrazol-4-yl]pyrrolidin-2-one (0.035 g, 0.095 mmol), 4-chloro-3-methyl-5-(trifluoromethyl)-1H-pyrazole (0.050 g, 0.27 mmol) and K2CO3 (0.050 g, 0.36 mmol) in DMF (0.8 mL) was stirred at 60° C. for 40 min. 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 (0.036 g, 78%). 1H NMR (400 MHz, CDCl3) δ 7.57 (s, 1H), 7.47 (m, 2H), 7.34 (m, 2H), 5.05 (dd, J=9.2, 6.0 Hz, 1H), 4.04 (m, 1H), 3.81 (m, 1H), 2.99 (heptet, J=6.8 Hz, 1H), 2.87 (m, 1H), 2.76 (m, 1H), 2.42 (s, 3H), 1.22 (d, J=7.2 Hz, 3H), 1.12 (d, J=7.2 Hz, 3H); MS: (ES) m/z calculated for C21H20Cl2F3N5O [M+H]+486.1. found 486.1.

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-aebbadaf7daa47489b9c2295ae4cb015
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328116B2

Reaction notes

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