Piconol → 5-Amino-1-(4-fluorophenyl)-4-[3-(pyridin-2-ylmethoxy)benzoyl]pyrazole

HRID 489851Notes

Reaction equation

HRID 489851 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]([OH:21])[CH:16]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH2:29]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1(C)C=CC=CC=1>[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]([O:21][CH2:29][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=2)[CH:16]=1

Participants

6

Reactant 4

HCID 11474PiconolHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 115439135-Amino-1-(4-fluorophenyl)4-[3-hydroxybenzoyl]pyrazole

Product 1

HCID 98650945-Amino-1-(4-fluorophenyl)-4-[3-(pyridin-2-ylmethoxy)benzoyl]pyrazole

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

5-Amino-1-(4-fluorophenyl)-4-[3-hydroxybenzoyl]pyrazole, from Example 10, step 2, (0.5 g, 1.68 mmol), 2-pyridylcarbinol (0.81 mL, 8.41 mmol), triphenylphosphine (1.81 g, 6.9 mmol), and diethylazodicarboxylate (1.09 mL, 6.9 mmol)) were combined in toluene (50 mL). The reaction mixture was stirred for 16 hours then quenched with a saturated aqueous solution of NH4Cl and extracted three times with ethyl acetate. The product was then extracted from the ethyl acetate into a 10% aqueous solution of HCl. The aqueous layer was then neutralized with NaOH and extracted with ethyl acetate. The organic extracts were dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by column chromatography on silica gel using 1:1 hexane/ethyl acetate to give 0.165 g of 5-amino-1-(4-fluorophenyl)-4-[3-(pyridin-2-ylmethoxy)benzoyl]pyrazole (mpt. 176.1-177.3° C.).

Workup

  1. customthen quenched with a saturated aqueous solution of NH4Cl
  2. extractionextracted three times with ethyl acetate
  3. extractionThe product was then extracted from the ethyl acetate into a 10% aqueous solution of HCl
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by column chromatography on silica gel using 1:1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-8e2bf5c5cc3047338fc54c5bafc5f81c
Source dataset
uspto-grants-2005_12
Patent number
US06979693B2

Reaction notes

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