Cesium carbonate → (1Z)-1-[3-(5-methyl-2-propan-2-ylphenyl)-4-oxo-1,3-thiazolidin-2-ylidene]-3-[1-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]propan-2-yl]urea

HRID 1772445Notes

Reaction equation

HRID 1772445 reaction equation
[N:1]([CH:4]([CH3:28])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:16]=[CH:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[N:13]=2)=[CH:8][CH:7]=1)=[C:2]=[O:3].[N-]=C=O.[CH:32]([C:35]1[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][C:36]=1[NH:42][C:43]([NH2:45])=[S:44])([CH3:34])[CH3:33].C(=O)([O-])[O-].[Cs+].[Cs+].[C:52]([O-])(=[O:54])[CH3:53].[Na+].BrCC(OC)=O>C(#N)C.C(O)C.C(OCC)(=O)C>[CH:32]([C:35]1[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][C:36]=1[N:42]1[C:52](=[O:54])[CH2:53][S:44]/[C:43]/1=[N:45]\[C:2]([NH:1][CH:4]([CH3:28])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:16]=[CH:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:26])([F:25])[F:27])=[CH:19][CH:18]=3)[N:13]=2)=[CH:8][CH:7]=1)=[O:3])([CH3:34])[CH3:33]

Participants

10

Reactant 6

HCID 10796Cesium carbonateHCID 60984Methyl bromoacetateHCID 105034IsocyanateHCID 517045Sodium AcetateHCID 893731681-(2-Isopropyl-5-methylphenyl)thioureaHCID 904040983-(4-(2-isocyanatopropyl)phenyl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole

Product 1

HCID 90404514(1Z)-1-[3-(5-methyl-2-propan-2-ylphenyl)-4-oxo-1,3-thiazolidin-2-ylidene]-3-[1-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]propan-2-yl]ureaYield 20.7%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-(4-(2-Isocyanatopropyl)phenyl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (C39) (0.17 g, 0.41 mmol) in acetonitrile (2 mL) was heated at 80° C. for 2 hours to ensure complete conversion to the isocyanate. The reaction was cooled and 1-(2-isopropyl-5-methylphenyl)thiourea (0.095 g, 0.46 mmol) and cesium carbonate (0.20 g, 0.60 mmol) were added. The reaction was stirred at room temperature for 3 days. The reaction was diluted with ethanol (2.5 mL) and sodium acetate (0.064 g, 0.78 mmol) and methyl 2-bromoacetate (0.05 mL, 0.53 mmol) were added. The reaction was heated at 65° C. for 2.5 hours. The reaction mixture was diluted with ethyl acetate and washed with water. The aqueous layer was extracted an additional time with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was loaded onto a Celite® cartridge and purified by flash column chromatography using 0-100% ethyl acetate/B, where B=1:1 dichloromethane/hexanes, as eluent to afford the title compound as an off-white solid (0.054 g, 20%).

Workup

  1. temperatureThe reaction was cooled
  2. additionwere added
  3. temperatureThe reaction was heated at 65° C. for 2.5 hours
  4. washwashed with water
  5. extractionThe aqueous layer was extracted an additional time with ethyl acetate
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-8eb4004cefd14123b0895f4dcbc31dbf
Source dataset
uspto-grants-2016_02
Patent number
US09249133B2

Reaction notes

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