Sodium Carbonate → 5-Methyl-1-[2'-(trifluoromethoxy)-1,1'-biphenyl-3-yl]-1H-pyrazole-3-carboxamide

HRID 733125Notes

Reaction equation

HRID 733125 reaction equation
C([C:3]1[C:4]([C:16]([NH2:18])=[O:17])=[N:5][N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11](Br)[CH:10]=2)[C:7]=1[CH3:8])C.[F:19][C:20]([F:32])([F:31])[O:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C(O)CC.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:8][C:7]1[N:6]([C:9]2[CH:10]=[C:11]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[O:21][C:20]([F:19])([F:32])[F:31])[CH:12]=[CH:13][CH:14]=2)[N:5]=[C:4]([C:16]([NH2:18])=[O:17])[CH:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27772042-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 69062233ethyl 1-(3-bromophenyl)-5-methyl-1H-pyrazole-3-carboxamide

Product 1

HCID 99508045-Methyl-1-[2'-(trifluoromethoxy)-1,1'-biphenyl-3-yl]-1H-pyrazole-3-carboxamideYield 93.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 22495535HCID 22495535, compoundSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of ethyl 1-(3-bromophenyl)-5-methyl-1H-pyrazole-3-carboxamide (0.237 g, 0.8 mmol) and 2-trifluoromethoxyphenyl boronic acid (0.262 g, 1.2 mmol) in n-propanol/toluene (1.27 ml:0.42 ml) mixture were added tetrakis(triphenylphosphine)palladium (0.019 g, 0.01 mmol) and 2M sodium carbonate (0.84 ml). The reaction mixture was heated at 90° C. for 16 hours, and then cooled and partitioned between ethyl acetate and water. The organic phase was washed with saturated sodium bicarbonate and brine, then dried over sodium sulfate and concentrated. The crude product was purified by silica-gel column chromatography (3.5:1.5 hexanes/acetone) to give the product (0.270 g, 88%) as a solid.

Workup

  1. temperaturecooled
  2. custompartitioned between ethyl acetate and water
  3. washThe organic phase was washed with saturated sodium bicarbonate and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by silica-gel column chromatography (3.5:1.5 hexanes/acetone)

Sources & evidence

ORD record
ord-81c0a498528944c4a627c9d2b4bdaf35
Source dataset
uspto-grants-2009_09
Patent number
US07589116B2

Reaction notes

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