2,6-Difluoro-N-(1-{[4-iodo-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)benzamide → 2,6-Difluoro-N-(1-{[4-(2-methylpropyl)-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)benzamide

HRID 1946396Notes

Reaction equation

[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16](I)=[CH:15][C:14]=2[C:20]([F:23])([F:22])[F:21])[N:8]=1)=[O:5].[Br-].[C:30]([Zn+])([CH3:33])([CH3:32])[CH3:31]>C1COCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([CH2:31][CH:30]([CH3:33])[CH3:32])=[CH:15][C:14]=2[C:20]([F:23])([F:22])[F:21])[N:8]=1)=[O:5]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 2,6-difluoro-N-(1-{[4-iodo-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)benzamide (for a preparation see Example 73)(75 mg, 0.148 mmol) in THF (1 ml) was added tetrakis(triphenyl-phosphine)palladium (0) (17.1 mg, 0.015 mmol, Aldrich). To the solution was added 0.5 M t-butylzinc bromide in THF (0.6 ml, 0.30 mmol, Aldrich) and the mixture stirred at 80° C. under nitrogen for 3 h. A further amount of tetrakis (triphenylphosphine) palladium (0) (30 mg) and then 0.5 M t-butylzinc bromide in THF (1 ml, 0.5 mmol) was added to the mixture at ambient temperature. The mixture was heated to 80° C. for a further 3 h. The solvent was removed in vacuo and the residue dissolved in 1:1 MeOH:DMSO ml×2 and purified by MDAP on Sunfire C18 column (Method B) using Acetonitrile-Water with a Formic acid modifier. The solvent was evaporated in vacuo to give the title compound as a brown gum (12 mg); LCMS: (System 4) MH+=438, tRET=3.47 min.

Workup

temperatureThe mixture was heated to 80° C. for a further 3 h
customThe solvent was removed in vacuo
dissolutionthe residue dissolved in 1:1 MeOH
customDMSO ml×2 and purified by MDAP on Sunfire C18 column (Method B)
customThe solvent was evaporated in vacuo

Sources & evidence

ORD record: ord-83e80e20fd5e4480b639bec663023aa5
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399436B2

Reaction notes

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