Triethylamine → 2-[5-(4-chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazol-3-yl]-5,5-dimethyl-3,5-dihydro-imidazol-4-one

HRID 1805201Notes

Reaction equation

HRID 1805201 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:21](O)=O)[C:9]=2[CH3:24])=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.Cl.[NH2:32][C:33]([CH3:38])([CH3:37])[C:34]([NH2:36])=[O:35].C(N(CC)CC)C.O=P(Cl)(Cl)Cl>C1(C)C=CC=CC=1.C1COCC1.ClCCl.O.CN(C=O)C>[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:21]3[NH:36][C:34](=[O:35])[C:33]([CH3:38])([CH3:37])[N:32]=3)[C:9]=2[CH3:24])=[CH:4][CH:3]=1

Participants

11

Reactant 5

HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 65578Oxalyl chlorideHCID 15194215-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acidHCID 145690092-Amino-2-methylpropanamide hydrochloride

Product 1

HCID 441916922-[5-(4-chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazol-3-yl]-5,5-dimethyl-3,5-dihydro-imidazol-4-oneYield 53%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4a (1.01 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 mixture was allowed to warm to room temperature and stirred for 2 h, then transferred slowly to a mixture of 5i (0.56 g, 4.07 mmol) and triethylamine (0.42 g, 4.20 mmol) in THF (120 mL) at 0° C. After the mixture was warmed and stirred at room temperature for 15 h, water was added 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 crude amide (1.02 g) thus obtained was treated with a solution of POCl3 (1.25 g, 8.15 mmol) in dichloromethane (25 mL) at 80° C. for 4 h. The mixture was concentrated and poured into ice water. The resulting mixture was extracted with ethyl acetate (2×50 mL). The combined extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel with ethyl acetate/hexanes (7:3) afforded 23 (0.62 g, 53%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.43 (br s, 1H), 7.32˜7.27 (m, 4H), 7.05 (d, 2H), 7.00 (br s, 1H), 2.38 (s, 3H), 1.81 (s, 6H); ESMS m/z: 447.0 (M+1).

Workup

  1. customat 0° C.
  2. temperatureAfter the mixture was warmed
  3. stirringstirred at room temperature for 15 h
  4. extractionthe resulting mixture was extracted with ethyl acetate (2×30 mL)
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude amide (1.02 g) thus obtained
  10. concentrationThe mixture was concentrated
  11. additionpoured into ice water
  12. extractionThe resulting mixture was extracted with ethyl acetate (2×50 mL)
  13. washThe combined extracts were washed with brine
  14. dry with materialdried over anhydrous sodium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customPurification of the residue by flash chromatography on silica gel with ethyl acetate/hexanes (7:3)

Sources & evidence

ORD record
ord-f5fc56ea842b4b84bede09e561dd8cc3
Source dataset
uspto-grants-2013_01
Patent number
US08354442B2

Reaction notes

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