Methyl iodide → HCID 66704170, compound

HRID 424836Notes

Reaction equation

HRID 424836 reaction equation
[CH2:1]([O:3][C:4](=[O:38])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]3[N:22]([C:29]4[C:34]([Cl:35])=[CH:33][CH:32]=[CH:31][C:30]=4[Cl:36])[N:23]=[N:24][C:25]=3[CH:26]([CH3:28])[CH3:27])=[CH:15][C:14]=2[CH3:37])[CH:6]=1)[CH3:2].[H-].[Na+].I[CH3:42]>CN(C)C=O>[CH2:1]([O:3][C:4](=[O:38])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([N:11]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]3[N:22]([C:29]4[C:30]([Cl:36])=[CH:31][CH:32]=[CH:33][C:34]=4[Cl:35])[N:23]=[N:24][C:25]=3[CH:26]([CH3:27])[CH3:28])=[CH:15][C:14]=2[CH3:37])[CH3:42])[CH:6]=1)[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodide3×HCID 24758Sodium hydrideHCID 66704167HCID 66704167, compound

Product 1

HCID 66704170HCID 66704170, compoundYield 12.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 3-{4-[3-(2,6-dichloro-phenyl)-5-isopropyl-3H-[1,2,3]triazol-4-ylmethoxy]-2-methyl-benzylamino}-benzoic acid ethyl ester (160 mg, 0.29 mmol) and sodium hydride (13 mg, 0.33 mmol) in anhydrous N,N-dimethyl formamide is added iodomethane (50 mg, 0.35 mmol). After three hours, more iodomethane (50 mg, 0.35 mmol) is added and the mixture is heated to 60° C. After three hours, more iodomethane (50 mg, 0.35 mmol) is added and the mixture is stirred at room temperature over night. The mixture is then partitioned between diethylether and water. The aqueous layer is extracted three times with diethylether. The combined ether layers are dried (MgSO4) and concentrated under reduced pressure. The crude residue is purified on 12 g of silica with ethyl acetate in heptane gradient to provide 3-({4-[3-(2,6-Dichloro-phenyl)-5-isopropyl-3H-[1,2,3]triazol-4-ylmethoxy]-2-methyl-benzyl}-methyl-amino)-benzoic acid ethyl ester (20 mg, 12%) LC-MS: 567.0 (M+1).

Workup

  1. waitAfter three hours
  2. customThe mixture is then partitioned between diethylether and water
  3. extractionThe aqueous layer is extracted three times with diethylether
  4. dry with materialThe combined ether layers are dried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue is purified on 12 g of silica with ethyl acetate in heptane gradient

Sources & evidence

ORD record
ord-7179405d55a9490ab9600fafa05c4d49
Source dataset
uspto-grants-2012_01
Patent number
US08106077B2

Reaction notes

Loading…