Water → HCID 67452962, compound

HRID 1754565Notes

Reaction equation

HRID 1754565 reaction equation
C([O-])(=[O:3])C.[K+].Cl[C:7]1[C:8](F)=[CH:9][C:10](I)=[C:11](N(CC(F)(F)F)C(C2C=NN([CH:21]3[CH2:26]C[CH2:24][CH2:23][O:22]3)C=2)=O)[CH:12]=1.O>CN(C=O)C.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>[CH:7]1[CH2:8][CH2:9][CH2:10][CH2:11][CH:12]=1.[CH3:26][C:21](=[O:3])[O:22][CH2:23][CH3:24]

Participants

6

Reactant 3

HCID 962WaterHCID 517044Potassium Acetate2×HCID 86679809HCID 86679809, compound

Product 1

HCID 67452962HCID 67452962, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

The catalyst Pd(PPh3)4 (630 mg, 0.55 mmol) and potassium acetate (890 mg, 9.0 mmol) are added to a solution of N-(5-chloro-4-fluoro-2-iodophenyl)-1-(tetrahydro-2H-pyran-2-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxamide (2,2 g, 4.5 mmol) in 10 mL of anhydrous DMF placed in a microwave reactor under nitrogen. The reactor is sealed and the reaction mixture is stirred for 15 minutes at 90° C. under microwave irradiation. A further amount of catalyst Pd(PPh3)4 (630 mg, 0.55 mmol) and of potassium acetate (890 mg, 9.0 mmol) are added to the reaction medium, which is stirred for 15 minutes at 110° C. under microwave irradiation. The mixture is cooled, poured into water and extracted with EtOAc. The organic phase is washed with saturated aqueous NaCl solution, dried over Na2SO4 and concentrated to dryness. After purification by flash chromatography on silica (DCM/EtOAc: 100/0 to 95/5) and then (cyclohexene/EA: 90/10) and DCM (100%), 260 mg of a white solid are obtained (yield: 57%).

Workup

  1. customplaced in a microwave reactor under nitrogen
  2. customThe reactor is sealed
  3. stirringis stirred for 15 minutes at 110° C. under microwave irradiation
  4. temperatureThe mixture is cooled
  5. extractionextracted with EtOAc
  6. washThe organic phase is washed with saturated aqueous NaCl solution
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to dryness
  9. customAfter purification by flash chromatography on silica (DCM/EtOAc: 100/0 to 95/5)

Sources & evidence

ORD record
ord-d33c42ef93c749de96468610fb02a12e
Source dataset
uspto-grants-2015_10
Patent number
US09169246B2

Reaction notes

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