Water → 3-{2-methoxy-4-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-ylmethoxy]-phenyl}-4H-[1,2,4]oxadiazol-5-one

HRID 2263399Notes

Reaction equation

HRID 2263399 reaction equation
[OH:1][NH:2][C:3](=[NH:40])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[S:16][C:15]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)=[N:14][C:13]=2[CH2:27][N:28]2[CH2:33][CH2:32][CH:31]([C:34]([F:37])([F:36])[F:35])[CH2:30][CH2:29]2)=[CH:6][C:5]=1[O:38][CH3:39].N1C=CC=CC=1.[C:47]1([O:53]C(Cl)=O)C=CC=CC=1.O>ClCCl>[CH3:39][O:38][C:5]1[CH:6]=[C:7]([O:10][CH2:11][C:12]2[S:16][C:15]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:24])([F:25])[F:26])=[CH:19][CH:18]=3)=[N:14][C:13]=2[CH2:27][N:28]2[CH2:33][CH2:32][CH:31]([C:34]([F:37])([F:36])[F:35])[CH2:30][CH2:29]2)[CH:8]=[CH:9][C:4]=1[C:3]1[NH:40][C:47](=[O:53])[O:1][N:2]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 15891Phenyl chloroformateHCID 178493417HCID 178493417, compound

Product 1

HCID 1354414033-{2-methoxy-4-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-ylmethoxy]-phenyl}-4H-[1,2,4]oxadiazol-5-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 150 mg of N-hydroxy-2-methoxy-4-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-ylmethoxy]-benzamidine in 5 mL of anhydrous dichloromethane at 0° C. were dropwise added 50 μL of pyridine followed by 40 μL of phenylchloroformate. The resulting mixture was stirred at room temperature for 1 h then water and dichloromethane were added. The aqueous layer was separated and extracted with dichloromethane. The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. To a solution of the resulting residue in 2.7 mL of acetonitrile was added 60 μL of 1,8-diazabicyclo[5.4.0]undec-7-ene. The mixture was stirred at room temperature overnight. The solvent was removed under vacuo. The resulting residue was taken into tetrahydrofuran/ethyl acetate 50/50, washed with water, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (gradient from dichloromethane 100 to dichloromethane 90/methanol 10) to give 105 mg of 3-{2-methoxy-4-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-ylmethoxy]-phenyl}-4H-[1,2,4]oxadiazol-5-one.

Workup

  1. customat 0° C.
  2. customThe aqueous layer was separated
  3. extractionextracted with dichloromethane
  4. dry with materialThe combined organic extracts were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. additionTo a solution of the resulting residue in 2.7 mL of acetonitrile was added 60 μL of 1,8-diazabicyclo[5.4.0]undec-7-ene
  8. stirringThe mixture was stirred at room temperature overnight
  9. customThe solvent was removed under vacuo
  10. washwashed with water
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe crude product was purified by column chromatography on silica gel (gradient from dichloromethane 100 to dichloromethane 90/methanol 10)

Sources & evidence

ORD record
ord-374972c82c7844a9aaec59dd4e240f7c
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

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