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

HRID 924242Notes

Reaction equation

HRID 924242 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][C:5]=1[NH:11][C:12]([NH:14][C:15]([NH:17][CH2:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[N:31]=[CH:30][N:29]([C:32]3[CH:37]=[CH:36][C:35]([O:38][C:39]([F:42])([F:41])[F:40])=[CH:34][CH:33]=3)[N:28]=2)=[CH:23][CH:22]=1)=[O:16])=[S:13])([CH3:3])[CH3:2].[C:43]([O-])(=[O:45])[CH3:44].[Na+].C(O)C.BrCC(OC)=O>ClCCl>[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][C:5]=1[N:11]1[C:43](=[O:45])[CH2:44][S:13]/[C:12]/1=[N:14]\[C:15]([NH:17][CH2:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[N:31]=[CH:30][N:29]([C:32]3[CH:37]=[CH:36][C:35]([O:38][C:39]([F:41])([F:42])[F:40])=[CH:34][CH:33]=3)[N:28]=2)=[CH:23][CH:22]=1)=[O:16])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 702EthanolHCID 60984Methyl bromoacetateHCID 517045Sodium AcetateHCID 904044741-[(2-Isopropyl-5-methyl-phenyl)carbamothioyl]-3-[3-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]propyl]urea

Product 1

HCID 90404260(1Z)-1-[3-(5-methyl-2-propan-2-ylphenyl)-4-oxo-1,3-thiazolidin-2-ylidene]-3-[3-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]propyl]ureaYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

To 1-[(2-isopropyl-5-methyl-phenyl)carbamothioyl]-3-[3-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]propyl]urea (F21) (0.110 g, 0.184 mmol) in a 25 mL vial equipped with a stir bar and Vigreux column was added sodium acetate (0.0600 g, 0.735 mmol), ethanol (2 mL) and methyl bromoacetate (0.0250 mL, 0.276 mmol). The reaction was heated to 70° C. overnight. The reaction was cooled and diluted with dichloromethane. The layers were separated and the aqueous layer was extracted with dichloromethane. The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography using 0-30% ethyl acetate/B, where B=1:1 dichloromethane/hexanes, as eluent provided a solid which was dried overnight at 50° C. in vacuo to afford the title compound as a white solid (0.0791 g, 68%).

Workup

  1. temperatureThe reaction was cooled
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with dichloromethane
  4. additionThe organic layers were poured through a phase separator
  5. concentrationconcentrated
  6. customPurification by flash column chromatography
  7. customas eluent provided a solid which
  8. customwas dried overnight at 50° C. in vacuo

Sources & evidence

ORD record
ord-b2ce4b4d7d534ba1b13c5a9b8b401a48
Source dataset
uspto-grants-2016_03
Patent number
US09278964B2

Reaction notes

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