Sodium hydride → Ethyl 1-(6-{2-[(4-bromophenyl)(difluoro)methoxy]phenyl}pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

HRID 1255219Notes

Reaction equation

HRID 1255219 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:13]=[C:12]([N:14]2[C:18]([C:19]([F:22])([F:21])[F:20])=[C:17]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:16]=[N:15]2)[CH:11]=[CH:10][CH:9]=1.[H-].[Na+].[Br:30][C:31]1[CH:36]=[CH:35][C:34]([C:37](Br)([F:39])[F:38])=[CH:33][CH:32]=1>CN(C=O)C>[Br:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]([F:39])([F:38])[O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[C:8]2[N:13]=[C:12]([N:14]3[C:18]([C:19]([F:22])([F:21])[F:20])=[C:17]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:16]=[N:15]3)[CH:11]=[CH:10][CH:9]=2)=[CH:33][CH:32]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 223280691-Bromo-4-(bromodifluoromethyl)benzeneHCID 136298134Ethyl 1-[6-(2-hydroxylphenyl)pyridine-2-yl]-5-trifluoromethyl-1H-pyrazole-4-carboxylate

Product 1

HCID 86633499Ethyl 1-(6-{2-[(4-bromophenyl)(difluoro)methoxy]phenyl}pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cooled (0° C.) solution of the title compound from Example 1 Step B (515 mg, 1.37 mmol) in DMF (5 mL) was added NaH (35.0 mg, 1.46 mmol). The reaction vessel was then allowed to warm to ambient temperature for 25 min, followed by addition of 1-bromo-4-[bromo(difluoro)methyl]benzene (445 mg, 1.56 mmol, synthesized according to U.S. Pat. No. 6,939,990) and heated at 60° C. After 24 h, the reaction mixture was cooled, quenched by addition of 2 N HCl and extracted with hexane-EtOAc. Purification by silica gel flash chromatography (5% EtOAc in hexanes to 10% EtOAc in hexanes) yielded the title compound: LCMS m/z 564.1 [M−F]+; 1H NMR (400 MHz, CDCl3) δ 8.12 (s, 1H), 7.88-7.82 (m, 2H), 7.78 (d, J=7.1 Hz, 1H), 7.57 (dd, J=7.8, 0.7 Hz, 1H), 7.50 (d, J=8.5 Hz, 2H), 7.46-7.41 (m, 2H), 7.39-7.32 (m, 3H), 4.37 (q, J=7.1 Hz, 2H), 1.38 (t, J=7.1 Hz, 3H).

Workup

  1. customsynthesized
  2. temperature6,939,990) and heated at 60° C
  3. temperaturethe reaction mixture was cooled
  4. customquenched by addition of 2 N HCl
  5. extractionextracted with hexane-EtOAc
  6. customPurification by silica gel flash chromatography (5% EtOAc in hexanes to 10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-8e0441b3b6484d9d9cff01ff0547e894
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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