Potassium Permanganate → Ethyl 2-(3-methoxy-4-(6-methylpyridazin-4-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)-methyl)pyrimidine-4-carboxylate

HRID 59095Notes

Reaction equation

HRID 59095 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[C:10]([CH2:12][O:13][CH2:14][C:15]([F:18])([F:17])[F:16])[N:9]=[C:8]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[C:30]([CH3:32])[N:29]=[N:28][CH:27]=3)=[C:22]([O:33][CH3:34])[CH:21]=2)[N:7]=1)=C)[CH3:2].I([O-])(=O)(=O)=[O:36].[Na+].[Mn]([O-])(=O)(=O)=O.[K+].[K]>O1CCOCC1.O>[CH3:34][O:33][C:22]1[CH:21]=[C:20]([NH:19][C:8]2[N:7]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:36])[CH:11]=[C:10]([CH2:12][O:13][CH2:14][C:15]([F:18])([F:17])[F:16])[N:9]=2)[CH:25]=[CH:24][C:23]=1[C:26]1[CH:31]=[C:30]([CH3:32])[N:29]=[N:28][CH:27]=1

Participants

7

Reactant 4

HCID 516875Potassium PermanganateHCID 5462222PotassiumHCID 23667635Sodium periodateHCID 1178210484-(1-Ethoxyvinyl)-N-(3-methoxy-4-(6-methylpyridazin-4-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-2-amine

Product 1

HCID 117821334Ethyl 2-(3-methoxy-4-(6-methylpyridazin-4-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)-methyl)pyrimidine-4-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

4-(1-Ethoxyvinyl)-N-(3-methoxy-4-(6-methylpyridazin-4-yl)phenyl)-6-((2,2,2-trifluoroethoxy)-methyl)pyrimidin-2-amine (0.7 g, 1.47 mmol) was dissolved in 1,4-dioxane (50 mL). Sodium metaperiodate (0.630 g, 2.94 mmol) was suspended in water (25 mL) and sonicated until a clear solution was obtained then added to the dioxane-solution. Potassium permanganate (0.035 g, 0.22 mmol) was added and the mixture was stirred at rt. Additional 10-15 mg of potassium permangante was added every 10 min. After 45 min the reaction mixture was filtered and the filter was washed with EtOAc. To the filtrate were sodium bicarbonate (s) and sodium chloride (s) added and the mixture was stirred for 5 min. The phases were separated and aqueous layer was extracted with ethyl acetate (×2). The combined organic layer was dried over sodium sulfate, filtrated and evaporated. The residue was purified by column chromatography on silica eluting with a gradient of methanol in DCM to give the title compound as a solid, 595 mg (85%).

Workup

  1. customsonicated until a clear solution
  2. customwas obtained
  3. filtrationAfter 45 min the reaction mixture was filtered
  4. washthe filter was washed with EtOAc
  5. additionadded
  6. stirringthe mixture was stirred for 5 min
  7. customThe phases were separated
  8. extractionaqueous layer was extracted with ethyl acetate (×2)
  9. dry with materialThe combined organic layer was dried over sodium sulfate
  10. filtrationfiltrated
  11. customevaporated
  12. customThe residue was purified by column chromatography on silica eluting with a gradient of methanol in DCM

Sources & evidence

ORD record
ord-7c039f124bf240659c8805f51b47646c
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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