Pyridine → 5-(4-{2-[5-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-4-yl]-ethoxy}-phenyl)-3H-[1,3,4]oxadiazol-2-one

HRID 253208Notes

Reaction equation

HRID 253208 reaction equation
[CH3:1][C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:17][CH2:18][O:19][C:20]1[CH:29]=[CH:28][C:23]([C:24]([NH:26][NH2:27])=[O:25])=[CH:22][CH:21]=1.N1C=CC=CC=1.[C:36]1([O:42]C(Cl)=O)C=CC=CC=1.C1CCN2C(=NCCC2)CC1>ClCCl.C(OCC)(=O)C>[CH3:1][C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:17][CH2:18][O:19][C:20]1[CH:21]=[CH:22][C:23]([C:24]2[O:25][C:36](=[O:42])[NH:27][N:26]=2)=[CH:28][CH:29]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 579867444-{2-[5-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-4-yl]-ethoxy}-benzoic Acid Hydrazide

Product 1

HCID 113054015-(4-{2-[5-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-4-yl]-ethoxy}-phenyl)-3H-[1,3,4]oxadiazol-2-oneYield 47.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of: 4-{2-[5-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-4-yl]-ethoxy}-benzoic acid hydrazide (Example 4, 276 mg, 0.65 mmol) in dichloromethane (4 mL) add pyridine (104 μL, 1.3 mmol) followed by phenylchloroformate (0.88 μL, 0.71 mmol). Stir the resulting mixture at room temperature until all the starting material is consumed (by TLC analysis). Dilute the mixture with ethyl acetate wash with water then brine dry over MgSO4 and concentrate under reduced pressure. Take the residue up in acetonitrile (5 mL). To this mixture, add DBU (106 μL, 0.71 mmol). Seal the resulting solution; warm it to 170° C. in a Personal Chemistry™ microwave oven and stir at this temperature for 120 min. Cool the reaction to room temperature, dilute with ethyl acetate, wash with 1 M HCl solution (or saturated NaH2PO4 solution) dry over MgSO4 and concentrate. Triturate the resulting residue with dichloromethane several times to give the title compound as a tan solid (137 mg). (recrystallized from ethyl acetate in a sealed tube at 140° C.).

Workup

  1. customis consumed (by TLC analysis)
  2. additionDilute the mixture with ethyl acetate
  3. washwash with water
  4. dry with materialbrine dry over MgSO4
  5. concentrationconcentrate under reduced pressure
  6. customSeal the resulting solution
  7. temperaturewarm it to 170° C. in a Personal Chemistry™ microwave oven
  8. stirringstir at this temperature for 120 min
  9. temperatureCool
  10. customthe reaction to room temperature
  11. washwash with 1 M HCl solution (or saturated NaH2PO4 solution)
  12. dry with materialdry over MgSO4
  13. concentrationconcentrate
  14. customTriturate the resulting residue with dichloromethane several times

Sources & evidence

ORD record
ord-8e16b9e069a94869b64e695ec6d2fc3a
Source dataset
uspto-grants-2011_01
Patent number
US07872032B2

Reaction notes

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