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

HRID 924202Notes

Reaction equation

HRID 924202 reaction equation
[F:1][C:2]([F:30])([F:29])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH:21]([CH3:28])[CH2:22]C(N=[N+]=[N-])=O)=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.[CH:31]([C:34]1[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][C:35]=1[NH:41][C:42]([NH2:44])=[S:43])([CH3:33])[CH3:32].[C:45](=[O:48])([O-])[O-].[Cs+].[Cs+].[C:51]([O-:54])(=O)[CH3:52].[Na+].BrCC(OC)=O.C(#[N:64])C>C(OCC)(=O)C.C(O)C>[CH:31]([C:34]1[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][C:35]=1[N:41]1[C:51](=[O:54])[CH2:52][S:43]/[C:42]/1=[N:44]\[C:45]([NH:64][CH2:22][CH:21]([C:18]1[CH:19]=[CH:20][C:15]([C:12]2[N:13]=[CH:14][N:10]([C:7]3[CH:8]=[CH:9][C:4]([O:3][C:2]([F:29])([F:1])[F:30])=[CH:5][CH:6]=3)[N:11]=2)=[CH:16][CH:17]=1)[CH3:28])=[O:48])([CH3:33])[CH3:32]

Participants

9

Reactant 6

HCID 6342AcetonitrileHCID 10796Cesium carbonateHCID 60984Methyl bromoacetateHCID 517045Sodium AcetateHCID 893731681-(2-Isopropyl-5-methylphenyl)thioureaHCID 904042293-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)butanoyl azide

Product 1

HCID 90404418(1Z)-1-[3-(5-methyl-2-propan-2-ylphenyl)-4-oxo-1,3-thiazolidin-2-ylidene]-3-[2-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]propyl]ureaYield 35%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-(4-(1-(4-(Trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)butanoyl azide (C42) (0.22 g, 0.52 mmol) in acetonitrile (2.6 mL) was heated at 80° C. for 2 hours. The reaction was cooled and 1-(2-isopropyl-5-methylphenyl)thiourea (0.12 g, 0.57 mmol) and cesium carbonate (0.20 g, 0.61 mmol) were added. The reaction was stirred at room temperature for 18 hours. Sodium acetate (0.093 g, 1.1 mmol), methyl 2-bromoacetate (0.07 mL, 0.78 mmol) and ethanol (2.6 mL) were added, and the reaction mixture was heated at 65° C. for 3 hours. The reaction was cooled, diluted with ethyl acetate, and washed with water. The aqueous layer was extracted once more 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 orange solid (0.12 g, 35%).

Workup

  1. temperatureThe reaction was cooled
  2. temperaturethe reaction mixture was heated at 65° C. for 3 hours
  3. temperatureThe reaction was cooled
  4. washwashed with water
  5. extractionThe aqueous layer was extracted once more 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-7301dff9a93e4130b1c370dfa2af4621
Source dataset
uspto-grants-2016_03
Patent number
US09278964B2

Reaction notes

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