Dimethylformamide → HCID 67215163, compound

HRID 2421140Notes

Reaction equation

HRID 2421140 reaction equation
[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[C:13]1[O:17][C:16]([C:18]2[CH:27]=[CH:26]C3N[C:23](=O)[NH:24][C:20]=3[CH:19]=2)=[N:15][N:14]=1.IC.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:40][N:41]([CH:43]=[O:44])[CH3:42]>C(OCC)(=O)C>[CH3:40][N:41]1[C:42]2[CH:26]=[CH:27][C:18]([C:16]3[O:17][C:13]([C:3]4[C:4]([C:7]5[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=5)=[N:5][O:6][C:2]=4[CH3:1])=[N:14][N:15]=3)=[CH:19][C:20]=2[N:24]([CH3:23])[C:43]1=[O:44]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 6328Methyl iodide3×HCID 3251421Potassium bis(trimethylsilyl)amide2×HCID 67215347HCID 67215347, compound

Product 1

HCID 67215163HCID 67215163, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

5-[5-(5-Methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-1,3-dihydro-benzoimidazol-2-one (200 mg, 0.56 mmol) was heated in DMF (2 mL) until the suspension turned into solution. After the solution was cooled to ambient temperature iodomethane (38 μL, 0.61 mmol) was added and stirred for 18 h at this temperature. The resulting suspension was diluted with DMF (2 mL) and warmed until the reaction mixture became homogeneous. A solution of potassium bis(trimethylsilyl)amide (0.91 M in THF, 673 μL, 0.61 mmol) was added and stirred for 1 h at ambient temperature. Additional iodomethane (38 μL, 0.61 mmol) was added and stirring was continued for another 18 h. Additional potassium bis(trimethylsilyl)amide (0.91 M in THF, 673 μL, 0.61 mmol) was added, stirred for 15 min at ambient temperature, treated with iodomethane (0.38 μL, 0.61 mmol) and stirred for 5 h at this temperature. The reaction mixture was diluted with ethyl acetate (20 mL) and washed with aqueous sodium carbonate (saturated, 20 mL), water (20 mL) and brine (20 mL). The combined aqueous layers were extracted with ethyl acetate (20 mL) and the combined organic layers were dried over sodium sulfate. Purification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=40:40:20 to 10:70:20) afforded the title compound (29 mg, 13%) as a white solid. MS: m/e=388.1 [M+H]+.

Workup

  1. additionwas added
  2. temperaturewarmed until the reaction mixture
  3. stirringstirred for 1 h at ambient temperature
  4. stirringstirring
  5. waitwas continued for another 18 h
  6. stirringstirred for 15 min at ambient temperature
  7. stirringstirred for 5 h at this temperature
  8. washwashed with aqueous sodium carbonate (saturated, 20 mL), water (20 mL) and brine (20 mL)
  9. extractionThe combined aqueous layers were extracted with ethyl acetate (20 mL)
  10. dry with materialthe combined organic layers were dried over sodium sulfate
  11. customPurification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=40:40:20 to 10:70:20)

Sources & evidence

ORD record
ord-c1b0f9380df34726928bc36a172d21d1
Source dataset
uspto-grants-2011_06
Patent number
US07956074B2

Reaction notes

Loading…