Water → N-[2-(isopropoxymethyl)phenyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-carboxamide

HRID 1176011Notes

Reaction equation

[H-].[Na+].[OH:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][C:12]([C:14]1[C:15]([C:20]([F:23])([F:22])[F:21])=[N:16][N:17]([CH3:19])[CH:18]=1)=[O:13].I[CH:25]([CH3:27])[CH3:26].O>CN(C)C=O.CO>[CH:25]([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][C:12]([C:14]1[C:15]([C:20]([F:23])([F:22])[F:21])=[N:16][N:17]([CH3:19])[CH:18]=1)=[O:13])([CH3:27])[CH3:26]

Participants

Conditions

Temperature: 100 °C

Procedure

156.0 mg (3.9 mmol) of 60% sodium hydride in oil are added to a solution of 897.8 mg (3.0 mmol) N-[2-(hydroxymethyl)phenyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide (IV-1) in 2 ml dimethyl formamide at room temperature. After 30 minutes, 0.6 ml (6.0 mmol) 2-iodopropane are added. The reaction mixture is stirred for 6 hours at 100° C. and thereafter for 16 hours at room temperature. Afterward, the mixture is diluted with 1 ml methanol, added to water and extracted with ethyl acetate; the organic phase is dried over magnesium sulfate, the drying agent filtered off and the material concentrated under vacuum. Column chromatography (3:1 cyclohexane/ethyl acetate) yielded 100.0 mg (9.7% of the theoretical yield) of N-[2-(isopropoxymethyl)phenyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-carboxamide [logP (pH 2.3)=2.85].

Workup

waitfor 16 hours at room temperature
extractionextracted with ethyl acetate
dry with materialthe organic phase is dried over magnesium sulfate
filtrationthe drying agent filtered off
concentrationthe material concentrated under vacuum
customColumn chromatography (3:1 cyclohexane/ethyl acetate) yielded 100.0 mg (9.7% of the

Sources & evidence

ORD record: ord-08b59c829b42495ba7201e6a5b92df67
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07842710B2

Reaction notes

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