Sodium Carbonate → 1-[4'-Fluoro-2'-(trifluoromethyl)-1,1'-biphenyl-3-yl]-5-methyl-1h-pyrazole-3-carboxamide

HRID 733131Notes

Reaction equation

HRID 733131 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.C([O-])(=O)C.[K+].Br[C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=1[C:32]([F:35])([F:34])[F:33].C(=O)([O-])[O-].[Na+].[Na+]>CS(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:31][C:28]1[CH:29]=[CH:30][C:25]([C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([N:6]3[C:7]([CH3:8])=[CH:3][C:4]([C:16]([NH2:18])=[O:17])=[N:5]3)[CH:10]=2)=[C:26]([C:32]([F:33])([F:34])[F:35])[CH:27]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 5209832-Bromo-5-fluorobenzotrifluorideHCID 69062233ethyl 1-(3-bromophenyl)-5-methyl-1H-pyrazole-3-carboxamide

Product 1

HCID 114171631-[4'-Fluoro-2'-(trifluoromethyl)-1,1'-biphenyl-3-yl]-5-methyl-1h-pyrazole-3-carboxamideYield 41%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of ethyl 1-(3-bromophenyl)-5-methyl-1H-pyrazole-3-carboxamide (from step 2 of EXAMPLE 1) (0.069 g, 0.24 mmol) in DMSO (1.14 mL), bis(pinacoloato)diboron (0.075 g, 0.3 mmol) was added followed by potassium acetate (0.072 g, 0.74 mmol) and PdCl2(dppf)2 (0.005 g, 3 mol %). The solution was heated in a Smith Creator™ microwave reactor (commercially available from Personal Chemistry, Inc.) at 140° C. for 1200 seconds. The reaction mixture was cooled to room temperature, and 2-bromo-5-fluorobenzotrifluoride (0.12 g, 0.5 mmol), PdCl2(dppf)2 (0.005 g, 3 mol %) and 2M sodium carbonate (0.61 mL, 1.2 mmol) were added to the reaction mixture. The reaction was then subjected to microwave radiation at 140° C. for 2800 seconds. After cooling to room temperature, the reaction mixture was partitioned between EtOAc and water. The organic layer was washed with saturated sodium bicarbonate and brine, then dried over sodium sulfate, filtered and concentrated. Purification of the crude product by reverse phase HPLC (acetonitrile/water system) (gradient: 45% to 100% acetonitrile over 10 minutes) yielded 0.036 mg of the product (41% yield, retention time 5.1 minutes).

Workup

  1. temperatureThe solution was heated in a Smith Creator™ microwave reactor (commercially available from Personal Chemistry, Inc
  2. customat 140° C.
  3. customfor 2800 seconds
  4. temperatureAfter cooling to room temperature
  5. customthe reaction mixture was partitioned between EtOAc and water
  6. washThe organic layer was washed with saturated sodium bicarbonate and brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification of the crude product by reverse phase HPLC (acetonitrile/water system) (gradient: 45% to 100% acetonitrile over 10 minutes)

Sources & evidence

ORD record
ord-337a3bc5ca0a46a6a8bace89eaf0c5be
Source dataset
uspto-grants-2009_09
Patent number
US07589116B2

Reaction notes

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