Aniline → HCID 1481283, compound

HRID 1624561Notes

Reaction equation

HRID 1624561 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Al](C)C.[O:12]=[C:13]1[CH:18]=[CH:17][N:16]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)[N:15]=[C:14]1[C:29]([O:31]C)=O>C(Cl)Cl>[O:12]=[C:13]1[CH:18]=[CH:17][N:16]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:26])([F:27])[F:28])[CH:20]=2)[N:15]=[C:14]1[C:29]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:31]

Participants

5

Reactant 3

HCID 6115AnilineHCID 1481306HCID 1481306, compoundHCID 16682925Trimethylaluminum

Product 1

HCID 1481283HCID 1481283, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of aniline (0.360 mL, 3.95 mmol) in methylene chloride (10 mL) was cooled on an ice water bath then treated with a solution of trimethyl aluminum (2 M in toluene, 2.0 mL, 4.0 mmol). After the addition was complete, the reaction was allowed to warm to room temperature and stirred for 30 min. At that point, methyl 4-oxo-1-[3-(trifluoromethyl)phenyl]-1,4-dihydropyridazine-3-carboxylate (0.595 g, 2.00 mmol) was added and the reaction was heated at reflux for 18 h. After that time, the reaction was cooled to room temperature and carefully quenched with HCl aqueous solution (1 N, 5 mL). The organic layer was separated and the aqueous layer was extracted with methylene chloride (3×10 mL). The combined organic extracts were washed with saturated NaHCO3 aqueous solution (50 mL) and brine (50 mL), dried (MgSO4), and concentrated. The residue was recrystallized from ethyl acetate/hexanes to give 0.214 g (30%) of 4-Oxo-N-phenyl-1-[3-(trifluoromethyl)phenyl]-1,4-dihydropyridazine-3-carboxamide as yellow crystals.

Workup

  1. additionAfter the addition
  2. temperaturethe reaction was heated
  3. temperatureat reflux for 18 h
  4. temperatureAfter that time, the reaction was cooled to room temperature
  5. customcarefully quenched with HCl aqueous solution (1 N, 5 mL)
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with methylene chloride (3×10 mL)
  8. washThe combined organic extracts were washed with saturated NaHCO3 aqueous solution (50 mL) and brine (50 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. customThe residue was recrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-9254f978f922476d8b3c7cea2ec488ed
Source dataset
uspto-grants-2014_07
Patent number
US08778944B2

Reaction notes

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