Triethylamine → 4H-Imidazol-4-one, 2-[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]-1,5-dihydro-1,5,5-trimethyl-

HRID 1805190Notes

Reaction equation

HRID 1805190 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10](C(O)=O)[C:9]=2[CH3:24])=[CH:4][CH:3]=1.[C:25](Cl)(=O)C(Cl)=O.[CH3:31][C:32]([NH:37][CH3:38])([CH3:36])[C:33]([NH2:35])=[O:34].C(N(CC)CC)C.C[O-].[Na+]>C1(C)C=CC=CC=1.C1COCC1.CO.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:38]3[N:37]([CH3:25])[C:32]([CH3:36])([CH3:31])[C:33](=[O:34])[N:35]=3)[C:9]=2[CH3:24])=[CH:6][CH:7]=1

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 15194215-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acidHCID 10942334Sodium MethoxideHCID 186829772-Methyl-2-(methylamino)propanamide

Product 1

HCID 441917474H-Imidazol-4-one, 2-[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]-1,5-dihydro-1,5,5-trimethyl-Yield 55.4%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4a (1.0 g, 2.62 mmol) in toluene (30 mL) at 0° C. were sequentially added DMF (0.2 mL) and oxalyl chloride (1.48 g, 11.66 mmol) dropwise. The resulting mixture was allowed to warm to room temperature and stirred for 1 h, then transferred slowly to a mixture of 5a (0.50 g, 4.30 mmol) and triethylamine (0.42 g, 4.16 mmol) in THF (30 mL) at 0° C. After the mixture was warmed and stirred at room temperature for 15 h, the reaction was quenched with water and extracted with ethyl acetate (2×30 mL). The combined extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude residue (1.22 g), which without purification, underwent intramolecular cyclization by treatment with sodium methoxide (270 mg, 5.00 mmol) in methanol (30 mL) at 60° C. for 4 h. After the reaction was complete, the reaction mixture was concentrated and poured into ice water and the resulting mixture was extracted with ethyl acetate (2×30 mL). The combined extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel with hexanes/ethyl acetate (1:1) to afford the desired product 6 (0.67 g, 55%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.41 (d, 1H), 7.25 (d, 2H), 7.22 (dd, 1H), 7.12 (d, 1H), 7.01 (d, 2H), 3.42 (s, 3H), 2.35 (s, 3H), 1.37 (s, 6H); ESMS m/z: 461.0 (M+1).

Workup

  1. customat 0° C.
  2. temperatureAfter the mixture was warmed
  3. stirringstirred at room temperature for 15 h
  4. customthe reaction was quenched with water
  5. extractionextracted with ethyl acetate (2×30 mL)
  6. washThe combined extracts were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give the crude residue (1.22 g), which
  11. concentrationthe reaction mixture was concentrated
  12. additionpoured into ice water
  13. extractionthe resulting mixture was extracted with ethyl acetate (2×30 mL)
  14. washThe combined extracts were washed with brine
  15. dry with materialdried over anhydrous sodium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated
  18. customThe residue was purified by flash chromatography on silica gel with hexanes/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-8fd5792cfaa0407d8b2f09300da87899
Source dataset
uspto-grants-2013_01
Patent number
US08354442B2

Reaction notes

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