4-Fluorobenzohydrazide → 2-{4-chloro-1-{1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-(E)-methylidene}butyl}-5-(4-fluorophenyl)[1,3,4]oxadiazole

HRID 599660Notes

Reaction equation

HRID 599660 reaction equation
C(N(C(C)C)CC)(C)C.C1C=CC2N(O)N=NC=2C=1.FC(F)(F)C(O)=O.[Cl:27][CH2:28][CH2:29][CH2:30]/[C:31](=[CH:35]\[C:36]1[CH:41]=[CH:40][C:39]([N:42]2[CH:46]=[C:45]([CH3:47])[N:44]=[CH:43]2)=[C:38]([O:48][CH3:49])[CH:37]=1)/[C:32]([OH:34])=O.[F:50][C:51]1[CH:60]=[CH:59][C:54]([C:55]([NH:57][NH2:58])=O)=[CH:53][CH:52]=1.C(=O)(O)[O-].[Na+]>CN(C=O)C.C(OCC)(=O)C.C(Cl)CCl>[Cl:27][CH2:28][CH2:29][CH2:30]/[C:31](/[C:32]1[O:34][C:55]([C:54]2[CH:59]=[CH:60][C:51]([F:50])=[CH:52][CH:53]=2)=[N:57][N:58]=1)=[CH:35]\[C:36]1[CH:41]=[CH:40][C:39]([N:42]2[CH:46]=[C:45]([CH3:47])[N:44]=[CH:43]2)=[C:38]([O:48][CH3:49])[CH:37]=1

Participants

9

Reactant 5

HCID 99724-FluorobenzohydrazideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 66960186(E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetate

Product 1

HCID 670672392-{4-chloro-1-{1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-(E)-methylidene}butyl}-5-(4-fluorophenyl)[1,3,4]oxadiazoleYield 34.6%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

IPEA (1.2 mL), EDC (0.89 g) and HOBT (0.62 g) were added to a suspension of 5-chloro-2-{1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-(E)-methylidene}valeric acid trifluoroacetic acid salt (1.30 g) and 4-fluorobenzhydrazide (0.37 g) in DMF (25 mL) at room temperature, and the reaction solution was stirred at room temperature for two hours. A saturated sodium bicarbonate solution and ethyl acetate were added to the reaction solution, and the organic layer was separated. The organic layer was washed with a saturated sodium chloride solution, dried over magnesium sulfate and then concentrated under reduced pressure. A solution of the resulting residue in phosphorus oxychloride (6 mL) was heated under reflux for three hours. The reaction solution was left to cool to room temperature and concentrated under reduced pressure. A saturated sodium bicarbonate solution was added to the resulting residue, followed by extraction with chloroform. The resulting extract was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system) to obtain 376 mg of the title compound. The property value of the compound is as follows.

Workup

  1. customthe organic layer was separated
  2. washThe organic layer was washed with a saturated sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. temperatureA solution of the resulting residue in phosphorus oxychloride (6 mL) was heated
  6. temperatureunder reflux for three hours
  7. waitThe reaction solution was left
  8. temperatureto cool to room temperature
  9. concentrationconcentrated under reduced pressure
  10. additionA saturated sodium bicarbonate solution was added to the resulting residue
  11. extractionfollowed by extraction with chloroform
  12. extractionThe resulting extract
  13. dry with materialwas dried over magnesium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system)

Sources & evidence

ORD record
ord-1ba14f361b454f2db89a499044f5c9be
Source dataset
uspto-grants-2011_03
Patent number
US07897632B2

Reaction notes

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