Pyridine → 1-(4-methoxyphenyl)-5-[4-(1H-pyrrol-1yl)phenyl]-3-(trifluoro methyl)-1H-1,2,4-triazole

HRID 584736

Reaction equation

HRID 584736 reaction equation
[N:1]1([C:6]2[CH:14]=[CH:13][C:9]([C:10](O)=O)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[CH:2]1.C(Cl)(=O)C(Cl)=O.N1C=CC=CC=1.[F:27][C:28]([F:42])([F:41])[C:29](=[N:31][NH:32][C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=1)[NH2:30]>ClCCl.O1CCOCC1.CN(C)C=O>[CH3:40][O:39][C:36]1[CH:35]=[CH:34][C:33]([N:32]2[C:10]([C:9]3[CH:13]=[CH:14][C:6]([N:1]4[CH:5]=[CH:4][CH:3]=[CH:2]4)=[CH:7][CH:8]=3)=[N:30][C:29]([C:28]([F:27])([F:41])[F:42])=[N:31]2)=[CH:38][CH:37]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 27372564-(1H-Pyrrol-1-yl)benzoic acidHCID 696776222,2,2-trifluoro-N'-(4-methoxyphenyl)ethanehydrazonamide

Product 1

HCID 102000221-(4-methoxyphenyl)-5-[4-(1H-pyrrol-1yl)phenyl]-3-(trifluoro methyl)-1H-1,2,4-triazoleYield 12.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a suspension of 4-(1H-pyrrol-1yl)benzoic acid (337 mg, 1.8 mmol) in dichloromethane (3.5 mL), oxalyl chloride (0.157 mL, 1.8 mmol) and then dimethylformamide (10 microL) were added. The mixture was stirred overnight. The solvent was removed under reduced pressure. Pyridine (0.146 mL, 1.8 mmol) and a solution of 2,2,2-trifluoro-N′-(4-methoxyphenyl)ethanehydrazonamide (350 mg, 1.5 mmol) in 3.5 mL of dioxane were added to a suspension of the acyl chloride in 3.5 mL of dioxane. The mixture was refluxed with stirring for 3 hours. After cooling, the solvent was removed under reduced pressure and 0.1 N hydrochloric acid and dichloromethane were added to the residue. The organic layer was separated and the aqueous layer was extracted with dichloromethane. A combined layer was washed with 0.1 N hydrochloric acid and brine, and dried over magnesium sulfate. The solvent was removed under reduced pressure. The desired product was purified by silica gel column chromatography (hexane-ethyl acetate 8:1-5:1) to give 1-(4-methoxyphenyl)-5-[4-(1H-pyrrol-1yl)phenyl]-3-(trifluoromethyl)-1H-1,2,4-triazole (74 mg, 12.8% yield)

Workup

  1. customThe solvent was removed under reduced pressure
  2. temperatureThe mixture was refluxed
  3. stirringwith stirring for 3 hours
  4. temperatureAfter cooling
  5. customthe solvent was removed under reduced pressure and 0.1 N hydrochloric acid and dichloromethane
  6. additionwere added to the residue
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with dichloromethane
  9. washA combined layer was washed with 0.1 N hydrochloric acid and brine
  10. dry with materialdried over magnesium sulfate
  11. customThe solvent was removed under reduced pressure
  12. customThe desired product was purified by silica gel column chromatography (hexane-ethyl acetate 8:1-5:1)

Sources & evidence

ORD record
ord-486a064badbc40fb9bcfe0213c255bdc
Source dataset
uspto-grants-2005_08
Patent number
US06927230B2

Linked notes

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