Methyl iodide → HCID 91019241, compound

HRID 1242592Notes

Reaction equation

HRID 1242592 reaction equation
[CH3:1][O:2][N:3]=[C:4]1[CH2:8][C@@H:7]([C:9]2[N:13]=[C:12]([CH2:14][N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[O:11][N:10]=2)[N:6]([C:21]([C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:25][CH:24]=2)=[O:22])[CH2:5]1.[CH2:35](N(CC)CC)C.CI.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl>[CH3:1][O:2][N:3]=[C:4]1[CH2:8][C@@H:7]([C:9]2[N:13]=[C:12]([CH2:14][N:15]3[CH2:16][CH2:17][N:18]([CH3:35])[CH2:19][CH2:20]3)[O:11][N:10]=2)[N:6]([C:21]([C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:25][CH:24]=2)=[O:22])[CH2:5]1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 58714592HCID 58714592, compound

Product 1

HCID 91019241HCID 91019241, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution containing 1 equivalent of (3EZ,5S)-1-([1,1′-biphenyl]-4-ylcarbonyl)-5-[5-(1-piperazinylmethyl)-1,2,4-oxadiazol-3-yl]-3-pyrrolidinone O-methyloxime (Example 48), dissolved in dry DCM at 0° C. in presence of 1.5 equivalent of triethyl amine, was reacted with 1 equivalent of methyl iodide. The reaction mixture was stirred at room temperature for 12 hours. The reaction was hydrolyzed and then made basic with sodium carbonate solution (10%) and extracted with DCM. The organic phase was then dried with magnesium sulfate, and concentrated in vacuo to give a residue which was purified by flash-chromatography using dichloromethane/methanol as eluent to give the expected product, (3EZ,5S)-1-([1,1′-biphenyl]-4-ylcarbonyl)-5-{5-[(4-methyl-1-piperazinyl)methyl]-1,2,4-oxadiazol-3-yl}-3-pyrrolidinone O-methyloxime, as a mixture of E-/Z-isomers, in 50% yield (99.9% purity by HPLC). The pure Z-isomer could be separated by flash-chromatography, and was obtained in 31% yield (98.9% purity by HPLC).

Workup

  1. extractionextracted with DCM
  2. dry with materialThe organic phase was then dried with magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customto give a residue which
  5. customwas purified by flash-chromatography

Sources & evidence

ORD record
ord-b4875219b52642f58c17025baf698f88
Source dataset
uspto-grants-2006_10
Patent number
US07115639B2

Reaction notes

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