Potassium Hydroxide → 4-[4-cyclopropylaminomethyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl-4H-[1,2,4]oxadiazol-5-one

HRID 2263400Notes

Reaction equation

HRID 2263400 reaction equation
C1(OC(=O)[N:9]([CH:42]2[CH2:44][CH2:43]2)[CH2:10][C:11]2[N:12]=[C:13]([C:32]3[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=3)[S:14][C:15]=2[CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[NH:28][C:27](=[O:29])[O:26][N:25]=3)=[C:20]([O:30][CH3:31])[CH:19]=2)C=CC=CC=1.[OH-].[K+]>C(O)CO.O>[CH:42]1([NH:9][CH2:10][C:11]2[N:12]=[C:13]([C:32]3[CH:33]=[CH:34][C:35]([C:38]([F:40])([F:41])[F:39])=[CH:36][CH:37]=3)[S:14][C:15]=2[CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[NH:28][C:27](=[O:29])[O:26][N:25]=3)=[C:20]([O:30][CH3:31])[CH:19]=2)[CH2:43][CH2:44]1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 136149959HCID 136149959, compound

Product 1

HCID 1354463954-[4-cyclopropylaminomethyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl-4H-[1,2,4]oxadiazol-5-oneYield 35.9%

Reagents, catalysts & solvents 2

HCID 174Ethylene GlycolSolventHCID 962WaterSolvent

Procedure

To a solution of 32.6 mg of cyclopropyl-[5-[3-methoxy-4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-phenoxymethyl]-2-(4-trifluoromethyl-phenyl)-thiazol-4-ylmethyl]-carbamic acid phenyl ester in 2 mL of ethylene glycol was added 2 mL of a saturated solution of potassium hydroxide in water. The resulting mixture was stirred in a sealed tube under microwave irradiation for 25 minutes to 100° C., then 10 additional minutes to 120° C. and finally 15 more minutes to 140° C. It was then extracted with dichloromethane. The organic extracts were washed 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 9.5 mg of 3-{4-[4-cyclopropylaminomethyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl}-4H-[1,2,4]oxadiazol-5-one.

Workup

  1. customto 120° C.
  2. customto 140° C
  3. extractionIt was then extracted with dichloromethane
  4. washThe organic extracts were washed water
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. 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-77b56325181848b5a0be1a9ecd2a9b8f
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

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