Methyl iodide → HCID 59541728, compound

HRID 1928648Notes

Reaction equation

HRID 1928648 reaction equation
[CH3:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH:21]=[C:20]([NH:22][C:23](=[O:25])[CH3:24])[CH:19]=[N:18]2)=[CH:13][CH:12]=1.[H-].[Na+].I[CH3:29]>O1CCCC1.O>[CH3:29][N:22]([C:20]1[CH:19]=[N:18][N:17]([C:14]2[CH:15]=[CH:16][C:11]([O:10][CH2:9][CH2:8][CH2:7][N:3]3[CH2:4][CH2:5][CH2:6][C@H:2]3[CH3:1])=[CH:12][CH:13]=2)[CH:21]=1)[C:23](=[O:25])[CH3:24]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59541717HCID 59541717, compound

Product 1

HCID 59541728HCID 59541728, compoundYield 52.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-[1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazol-4-yl]acetamide obtained in Example 37 (0.34 g) in tetrahydrofuran (3.5 mL), sodium hydride (55% in mineral oil, 0.048 g) was added and iodomethane (0.225 g) was then added dropwise under ice cooling, followed by stirring at room temperature for 1.5 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by NH-type silica gel column chromatography (eluting solvent: ethyl acetate:hexane=1:1→ethyl acetate), and the resulting crystal was washed with diisopropyl ether to give the titled compound (0.187 g) as a white solid.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by NH-type silica gel column chromatography (eluting solvent: ethyl acetate:hexane=1:1→ethyl acetate)
  6. washthe resulting crystal was washed with diisopropyl ether

Sources & evidence

ORD record
ord-35a010b6a6be4988aa73e6b6b4d2e0fc
Source dataset
uspto-grants-2012_05
Patent number
US08183387B2

Reaction notes

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