Potassium Phosphate, Tribasic → 5-Amino-1-(4-fluorophenyl)-4-[3-(pyridin-3-yl)benzoyl]pyrazole

HRID 489831Notes

Reaction equation

HRID 489831 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14](=[O:22])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17](Br)[CH:16]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[C:25](B(O)O)[CH:24]=1.B1(C2C=CC=NC=2)OCCCO1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.[Cl-].[Na+].O>[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14](=[O:22])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:25]2[CH:24]=[N:23][CH:28]=[CH:27][CH:26]=2)[CH:16]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27343783-Pyridinylboronic acidHCID 41980053-(1,3,2-Dioxaborinan-2-yl)pyridineHCID 114512375-Amino4-(3-bromobenzoyl)-1-(4-fluorophenyl)pyrazole

Product 1

HCID 99506645-Amino-1-(4-fluorophenyl)-4-[3-(pyridin-3-yl)benzoyl]pyrazole

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 5-amino-4-(3-bromobenzoyl)-1-(4-fluorophenyl)pyrazole (0.9 g, 2.5 mmol) [prepared as described in Example 1 above], pyridine-3-boronic acid, 1,3-propanediol cyclic ester (0.5 g, 3 mmol), potassium phosphate (0.8 g, 3.73 mmol) and tetrakistriphosphine palladium (0.3 g, 0.25 mmol) in dioxane (20 ml) was heated at 85° C. under argon. After 16 h, the reaction mixture was cooled to room temperature and poured into brine. The product was extracted into ethyl acetate, dried over sodium sulfate and filtered. The organic layer was removed in vacuo and the residue was purified by flash chromatography (elution gradient: 40-80% ethyl acetate/hexane) to give 5-amino-1-(4-fluorophenyl)-4-[3-(pyridin-3-yl)benzoyl]pyrazole (0.50 g) which was recrystallized from ethyl acetate (mpt. 222.2-223.0).

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. extractionThe product was extracted into ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customThe organic layer was removed in vacuo
  6. customthe residue was purified by flash chromatography (elution gradient: 40-80% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-f9e79f097ffd47f197aedf3dcceed4b3
Source dataset
uspto-grants-2005_12
Patent number
US06979693B2

Reaction notes

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