Potassium Phosphate, Tribasic → HCID 89648401, compound

HRID 1484685Notes

Reaction equation

HRID 1484685 reaction equation
Br[C:2]1[CH:22]=[C:21]([F:23])[C:5]([CH2:6][N:7]2[C:11]([CH:12]3[CH2:14][CH2:13]3)=[C:10]([CH3:15])[C:9]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:8]2)=[C:4]([F:24])[CH:3]=1.[CH:25]1(B(O)O)[CH2:27][CH2:26]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH:12]1([C:11]2[N:7]([CH2:6][C:5]3[C:21]([F:23])=[CH:22][C:2]([CH:25]4[CH2:27][CH2:26]4)=[CH:3][C:4]=3[F:24])[N:8]=[C:9]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:10]=2[CH3:15])[CH2:14][CH2:13]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, Tribasic2×HCID 75806Tricyclohexylphosphine2×HCID 2760897Cyclopropylboronic acid2×HCID 89648172HCID 89648172, compound

Product 1

HCID 89648401HCID 89648401, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 962WaterSolvent3×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

1.0 g ethyl 1-(4-bromo-2,6-difluorobenzyl)-5-cyclopropyl-4-methyl-1H-pyrazole-3-carboxylate (2.51 mmol, 1.0 eq.) were dissolved in 40 mL toluene and 0.280 g cyclopropylboronic acid (3.26 mmol, 1.3 eq.), 1.86 g potassium phosphate (8.77 mmol, 3.5 eq.), 70 mg tricyclohexylphosphine (0.25 mmol, 0.10 eq.) and 0.66 mL water were added. The reaction mixture was flushed with nitrogen and 28 mg palladium acetate (0.125 mmol, 0.050 eq.) were added. The reaction mixture was stirred at 100° C. over night. Again 0.280 g cyclopropylboronic acid (3.26 mmol, 1.3 eq.), 1.86 g potassium phosphate (8.77 mmol, 3.5 eq.), 70 mg tricyclohexylphosphine (0.25 mmol, 0.10 eq.) and 0.66 mL water were added. The reaction mixture was flushed with nitrogen and 28 mg palladium acetate (0.125 mmol, 0.050 eq.) were added. The reaction mixture was stirred at 100° C. over night. Water was added and the aqueous phase was washed with ethyl acetate twice. The combined organic layers were dried over a silicon filter and concentrated in vacuo. The crude product was purified by flash chromatography to provide 652 mg (1.63 mmol, 65%) of the analytically pure target compound.

Workup

  1. additionwere added
  2. additionwere added
  3. stirringThe reaction mixture was stirred at 100° C. over night
  4. washthe aqueous phase was washed with ethyl acetate twice
  5. customThe combined organic layers were dried over a silicon
  6. filtrationfilter
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography
  9. customto provide 652 mg (1.63 mmol, 65%) of the analytically pure target compound

Sources & evidence

ORD record
ord-7253ef0ad77e43ad85ed8b0cb7bccdee
Source dataset
uspto-grants-2016_08
Patent number
US09422268B2

Reaction notes

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