Potassium Phosphate, Tribasic → HCID 89648401, compound

HRID 1774533Notes

Reaction equation

HRID 1774533 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-5cb080b8c6c5496db88144f30af45e01
Source dataset
uspto-grants-2016_02
Patent number
US09260412B2

Reaction notes

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