Water → 2-[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazol-3-yl]-3,5,5-trimethyl-3,5-dihydro-imidazol-4-one

HRID 1805205Notes

Reaction equation

HRID 1805205 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:14]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[Cl:22])[N:13]=[C:12]([C:23]3[NH:27][C:26](=[O:28])[C:25]([CH3:30])([CH3:29])[N:24]=3)[C:11]=2[CH3:31])=[CH:6][CH:5]=1.[CH3:32]I.O>CN(C=O)C>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:14]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[Cl:22])[N:13]=[C:12]([C:23]3[N:27]([CH3:32])[C:26](=[O:28])[C:25]([CH3:29])([CH3:30])[N:24]=3)[C:11]=2[CH3:31])=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 441916922-[5-(4-chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazol-3-yl]-5,5-dimethyl-3,5-dihydro-imidazol-4-one

Product 1

HCID 441918822-[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazol-3-yl]-3,5,5-trimethyl-3,5-dihydro-imidazol-4-oneYield 68.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of sodium hydride (14.4 mg, 0.66 mole) in DMF (3 mL) at 0° C. was added compound 23 (100 mg, 0.22 mmol) in one portion. The mixture was allowed to warm to room temperature and stirred for 30 min, at which time methyl iodide (2 g, 14.08 mmol) was added. After the mixture was stirred for 2 h, water was added and 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 crude residue by flash chromatography on silica gel with hexanes/ethyl acetate (1:1) gave the product 27 (70 mg, 0.15 mmol, 68%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.45 (d, 1H), 7.30 (d, 2H), 7.26 (dd, 1H), 7.18 (d, 1H), 7.07 (d, 2H), 3.28 (s, 3H), 2.24 (s, 3H), 1.87 (s, 6H); ESMS m/: 461.1 (M+1).

Workup

  1. additionwas added
  2. extractionthe resulting mixture was extracted with ethyl acetate (2×50 mL)
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the crude residue by flash chromatography on silica gel with hexanes/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-9c64077b249a43d285b3321f6cae5c78
Source dataset
uspto-grants-2013_01
Patent number
US08354442B2

Reaction notes

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