1,4-Dioxane → Ethyl 2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine-4-carboxylate

HRID 59072Notes

Reaction equation

HRID 59072 reaction equation
I([O-])(=O)(=O)=O.[Na+].[CH2:7]([O:9][C:10]([C:12]1[CH:17]=[C:16]([CH2:18][O:19][CH2:20][C:21]([F:24])([F:23])[F:22])[N:15]=[C:14]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([N:32]3[CH:36]=[C:35]([CH3:37])[N:34]=[CH:33]3)=[C:28]([O:38][CH3:39])[CH:27]=2)[N:13]=1)=C)[CH3:8].[O:40]1CCOCC1>O>[CH3:39][O:38][C:28]1[CH:27]=[C:26]([NH:25][C:14]2[N:13]=[C:12]([C:10]([O:9][CH2:7][CH3:8])=[O:40])[CH:17]=[C:16]([CH2:18][O:19][CH2:20][C:21]([F:23])([F:24])[F:22])[N:15]=2)[CH:31]=[CH:30][C:29]=1[N:32]1[CH:36]=[C:35]([CH3:37])[N:34]=[CH:33]1

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 23667635Sodium periodateHCID 1178242434-(1-Ethoxyvinyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-2-amine

Product 1

HCID 117823925Ethyl 2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of sodium metaperiodate (1.200 g, 5.61 mmol) and 4-(1-ethoxyvinyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-2-amine (1.3 g, 2.81 mmol) in a mixture of water (30 mL) and 1,4-dioxane (60 mL) potassium permanganate (0.066 g, 0.42 mmol) was added in portions of 10-15 mg in intervals of 5-8 min at ambient temperature. The mixture was filtered, the precipitate was washed with dioxane and ethyl acetate. Sodium bicarbonate and sodium chloride were added to the filtrate, the organic phase was separated, and the water phase was additionally extracted with ethyl acetate. The combined organic phase was dried over sodium sulfate and concentrated in vacuum. The residue was separated on a silica gel column using a gradient of 0-5% methanol in dichloromethane as eluent to yield the title product, 0.96 g (74%).

Workup

  1. additionwas added in portions of 10-15 mg in intervals of 5-8 min at ambient temperature
  2. filtrationThe mixture was filtered
  3. washthe precipitate was washed with dioxane and ethyl acetate
  4. additionSodium bicarbonate and sodium chloride were added to the filtrate
  5. customthe organic phase was separated
  6. extractionthe water phase was additionally extracted with ethyl acetate
  7. dry with materialThe combined organic phase was dried over sodium sulfate
  8. concentrationconcentrated in vacuum
  9. customThe residue was separated on a silica gel column

Sources & evidence

ORD record
ord-72ab9a47e7fa42338db26a64d598b65e
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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