Thiomorpholine → 4-{3-Methoxy-4-[5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-phenyl}-thiomorpholine

HRID 2421116Notes

Reaction equation

HRID 2421116 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([C:13]3[C:14]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[N:15][O:16][C:17]=3[CH3:18])=[N:11][N:12]=2)=[C:4]([O:25][CH3:26])[CH:3]=1.[NH:27]1[CH2:32][CH2:31][S:30][CH2:29][CH2:28]1>CS(C)=O>[CH3:26][O:25][C:4]1[CH:3]=[C:2]([N:27]2[CH2:32][CH2:31][S:30][CH2:29][CH2:28]2)[CH:7]=[CH:6][C:5]=1[C:8]1[O:9][C:10]([C:13]2[C:14]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[N:15][O:16][C:17]=2[CH3:18])=[N:11][N:12]=1

Participants

4

Reactant 2

HCID 67164ThiomorpholineHCID 167226452-(4-Fluoro-2-methoxy-phenyl)-5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazole

Product 1

HCID 167226464-{3-Methoxy-4-[5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-phenyl}-thiomorpholineYield 66.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
170 °C

Procedure

To a solution of 2-(4-fluoro-2-methoxy-phenyl)-5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazole (200 mg, 0.57 mmol) in DMSO (2 mL) was added thiomorpholine (0.29 mL, 2.85 mmol) and the reaction mixture was stirred for 5 h at 170° C. After cooling to ambient temperature it was extracted with water (20 mL) and ethyl acetate (20 mL). The aqueous layer was extracted with ethyl acetate (20 mL) and the combined organic layers were washed with brine (half-saturated, 20 mL) and aqueous sodium carbonate (saturated, 20 mL). Drying over sodium sulfate and purification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=70:10:20 to 40:40:20) afforded the title compound (164 mg, 66%) as an off-white solid. MS: m/e=435.3 [M+H]+.

Workup

  1. temperatureAfter cooling to ambient temperature it
  2. extractionwas extracted with water (20 mL) and ethyl acetate (20 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (20 mL)
  4. washthe combined organic layers were washed with brine (half-saturated, 20 mL) and aqueous sodium carbonate (saturated, 20 mL)
  5. dry with materialDrying over sodium sulfate and purification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=70:10:20 to 40:40:20)

Sources & evidence

ORD record
ord-5fd2e2e31b134b7892dd3ae6c770fa16
Source dataset
uspto-grants-2011_06
Patent number
US07956074B2

Reaction notes

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