Morpholine → 4-{4-[5-(5-Methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-pyridin-2-yl}-morpholine

HRID 1983133Notes

Reaction equation

HRID 1983133 reaction equation
Cl[C:2]1[CH:7]=[C:6]([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)[CH:5]=[CH:4][N:3]=1.[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1>CS(C)=O>[CH3:18][C:17]1[O:16][N:15]=[C:14]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]=1[C:10]1[O:9][C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:7]=2)=[N:12][N:11]=1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 866135792-Chloro-4-[5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-pyridine

Product 1

HCID 672153454-{4-[5-(5-Methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-pyridin-2-yl}-morpholineYield 72.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
170 °C

Procedure

To a solution of 2-chloro-4-[5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-pyridine (200 mg, 0.59 mmol) in DMSO (2 mL) was added morpholine (257 μL, 2.95 mmol) and stirred for 18 h under an argon atmosphere at 170° C. After cooling to ambient temperature the resulting dark brown solution was extracted with ethyl acetate (20 mL) and aqueous sodium carbonate (saturated, 20 mL). The aqueous layer was extracted with ethyl acetate (20 mL) and the combined organic layers were washed with water (20 mL) and brine (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 (166 mg, 72%) as a white solid. MS: m/e=390.1 [M+H]+.

Workup

  1. temperatureAfter cooling to ambient temperature the resulting dark brown solution
  2. extractionwas extracted with ethyl acetate (20 mL) and aqueous sodium carbonate (saturated, 20 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (20 mL)
  4. washthe combined organic layers were washed with water (20 mL) and brine (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-1f0ae69d7c6043789be39772a4ae5957
Source dataset
uspto-grants-2009_06
Patent number
US07541372B2

Reaction notes

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