Potassium Phosphate, Tribasic → HCID 89826224, compound

HRID 2206869Notes

Reaction equation

HRID 2206869 reaction equation
Br[C:2]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:3]=1[CH2:4][N:5]([CH:18]1[CH2:20][CH2:19]1)[C:6]([C:8]1[C:9]([CH:15]([F:17])[F:16])=[N:10][N:11]([CH3:14])[C:12]=1[Cl:13])=[O:7].[C:26]1(B(O)O)[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1.O>[Cl:13][C:12]1[N:11]([CH3:14])[N:10]=[C:9]([CH:15]([F:17])[F:16])[C:8]=1[C:6]([N:5]([CH2:4][C:3]1[CH:21]=[C:22]([F:25])[CH:23]=[CH:24][C:2]=1[C:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]=1)[CH:18]1[CH2:20][CH2:19]1)=[O:7]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 38629021-Cyclohexenylboronic acidHCID 89827192HCID 89827192, compound

Product 1

HCID 89826224HCID 89826224, compoundYield 51.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 22272177Toluene waterSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 300 mg (0.68 mmol) of N-(2-bromo-5-fluorobenzyl)-5-chloro-N-cyclopropyl-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide in a 10/1 mixture of toluene/water degassed with argon, are successively added 190 mg (1.50 mmol) of cyclohex-1-en-ylboronic acid, 38 mg (0.137 mmol) of tricyclohexylphosphine, 15 mg (0.069 mmol) of palladium (II) acetate and 437 mg (2.06 mmol) of tri-potassium phosphate. The mixture is heated at 100° C. for 1 hour. The reaction mixture is cooled to ambient temperature. 1 mL of water is added to the reaction mixture and the organic phase is filtered over a cake of diatomaceous earth. The cake is washed twice by dichloromethane and the combined organic phases are concentrated under vacuum to give 516 mg of crude material. A purification by column chromatography on silica gel (gradient heptane/ethyl acetate) yields 154 mg (49% yield) of 5-chloro-N-[2-(cyclohex-1-en-1-yl)-5-fluorobenzyl]-N-cyclopropyl-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide: (M+H)=438.

Workup

  1. customdegassed with argon
  2. temperatureThe reaction mixture is cooled to ambient temperature
  3. filtrationthe organic phase is filtered over a cake of diatomaceous earth
  4. washThe cake is washed twice by dichloromethane
  5. concentrationthe combined organic phases are concentrated under vacuum
  6. customto give 516 mg of crude material
  7. customA purification by column chromatography on silica gel (gradient heptane/ethyl acetate)

Sources & evidence

ORD record
ord-d84f22adcbf74d8aa6c6a3a173b1cf03
Source dataset
uspto-grants-2016_06
Patent number
US09374998B2

Reaction notes

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