Triethylamine → 3-{2-methoxy-4-[4-(3-thiomorpholin-4-yl-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-4H-1,2,4-oxadiazol-5-one

HRID 2263438Notes

Reaction equation

HRID 2263438 reaction equation
O[CH2:2][CH2:3][CH2:4][C:5]1[N:6]=[C:7]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=2)[S:8][C:9]=1[CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[NH:22][C:21](=[O:23])[O:20][N:19]=2)=[C:14]([O:24][CH3:25])[CH:13]=1.[CH2:36]([N:38](CC)[CH2:39][CH3:40])[CH3:37].C[S:44](Cl)(=O)=O>CN(C)C=O>[CH3:25][O:24][C:14]1[CH:13]=[C:12]([O:11][CH2:10][C:9]2[S:8][C:7]([C:26]3[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=3)=[N:6][C:5]=2[CH2:4][CH2:3][CH2:2][N:38]2[CH2:39][CH2:40][S:44][CH2:37][CH2:36]2)[CH:17]=[CH:16][C:15]=1[C:18]1[NH:22][C:21](=[O:23])[O:20][N:19]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 1361499373-{4-[4-(3-hydroxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl}-4H-[1,2,4]oxadiazol-5-one

Product 1

HCID 1361499813-{2-methoxy-4-[4-(3-thiomorpholin-4-yl-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-4H-1,2,4-oxadiazol-5-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 50 mg of 3-{4-[4-(3-hydroxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl}-4H-[1,2,4]oxadiazol-5-one in 1.5 mL of dimethylformamide at 0° C. were added 0.015 mL of triethylamine and 0.008 mL of methanesulfonyl chloride. The resulting mixture was stirred at 0° C. for 30 minutes and then concentrated under reduced pressure, taken into dichloromethane, washed with water, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was dissolved in 4 mL of dimethylformamide. To the resulting solution were added 0.012 mL of thiomorpholine, 0.017 mL of diisopropylethyl amine and 29 mg of potassium iodide. The reaction mixture was heated to 90° C. for 10 minutes under microwave irradiation in a sealed tube. It was then concentrated under reduced pressure, taken into dichloromethane, washed with water, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (gradient of methanol in dichloromethane), triturated in acetonitrile and filtered to give 5.3 mg of 3-{2-methoxy-4-[4-(3-thiomorpholin-4-yl-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-4H-1,2,4-oxadiazol-5-one.

Workup

  1. concentrationconcentrated under reduced pressure
  2. washwashed with water
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe crude product was dissolved in 4 mL of dimethylformamide
  7. additionTo the resulting solution were added 0.012 mL of thiomorpholine, 0.017 mL of diisopropylethyl amine and 29 mg of potassium iodide
  8. temperatureThe reaction mixture was heated to 90° C. for 10 minutes under microwave irradiation in a sealed tube
  9. concentrationIt was then concentrated under reduced pressure
  10. washwashed with water
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by column chromatography on silica gel (gradient of methanol in dichloromethane)
  15. customtriturated in acetonitrile
  16. filtrationfiltered

Sources & evidence

ORD record
ord-ce67399088d54013b6a129f4c24c8e8d
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

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