1,1'-Carbonyldiimidazole → 1-(4-Methyl-5-(3-methyl-1,2,4-oxadiazol-5-yl)thiazol-2-yl)-3-(4-(trifluoromethyl)benzyl)imidazolidin-2-one

HRID 2067640Notes

Reaction equation

HRID 2067640 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([N:10]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)[C:11]2=[O:26])[S:5][C:6]=1[C:7](O)=[O:8].C(N1C=CN=C1)(N1C=CN=C1)=O.O[NH:40][C:41](=[NH:43])[CH3:42]>CN(C)C=O.C(OCC)(=O)C>[CH3:1][C:2]1[N:3]=[C:4]([N:10]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:24])([F:23])[F:25])=[CH:18][CH:17]=3)[C:11]2=[O:26])[S:5][C:6]=1[C:7]1[O:8][N:43]=[C:41]([CH3:42])[N:40]=1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 579199574-Methyl-2-(2-oxo-3-(4-(trifluoromethyl)benzyl)imidazolidin-1-yl)thiazole-5-carboxylic acidHCID 178465666HCID 178465666, compound2×

Product 1

HCID 580315321-(4-Methyl-5-(3-methyl-1,2,4-oxadiazol-5-yl)thiazol-2-yl)-3-(4-(trifluoromethyl)benzyl)imidazolidin-2-oneYield 15%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-methyl-2-(2-oxo-3-(4-(trifluoromethyl)benzyl)imidazolidin-1-yl)thiazole-5-carboxylic acid (0.39 g, 1.00 mmol) in N,N-dimethylformamide (10 mL) was added 1,1′-carbonyldiimidazole (0.24 g, 1.50 mmol). The reaction mixture was stirred at ambient temperature for 10 minutes, and N-hydroxyacetamidine (0.08 g, 1.1 mmol) was added. The stirring was continued at ambient temperature for 6 hours, and another portion of N-hydroxyacetamidine (0.08 g, 1.1 mmol) was added. The reaction mixture was heated for 23 hours at 110° C. and cooled to ambient temperature, diluted with ethyl acetate and washed with water and brine. The organic solution was dried over anhydrous sodium sulfate, and filtered and concentrated in vacuo. The residue was purified by column chromatography to afford the title compound in 15% yield (0.06 g): mp 163-164° C. (ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 7.60 (d, J=8.1 Hz, 2H), 7.41 (d, J=8.1 Hz, 2H), 4.55 (s, 2H), 4.15-4.09 (m, 2H), 3.51-3.45 (m, 2H), 2.68 (s, 3H), 2.41 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 170.8, 167.3, 160.5, 155.3, 154.5, 139.6, 128.5, 125.9, 125.8, 122.1, 109.0, 47.6, 42.1, 41.9, 17.5, 11.6; MS (ES+) m/z 424.1 (M+1).

Workup

  1. waitThe stirring was continued at ambient temperature for 6 hours
  2. temperatureThe reaction mixture was heated for 23 hours at 110° C.
  3. temperaturecooled to ambient temperature
  4. washwashed with water and brine
  5. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-99e5098892874cf784546c5b20489694
Source dataset
uspto-grants-2012_10
Patent number
US08293768B2

Reaction notes

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