Cesium carbonate → 4-(1-Ethoxyvinyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-2-amine

HRID 59071Notes

Reaction equation

HRID 59071 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[CH2:9])[CH:5]=[C:4]([CH2:13][O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:3]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][C:28]=1[N:29]1[CH:33]=[C:32]([CH3:34])[N:31]=[CH:30]1)[NH2:25].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH2:11]([O:10][C:8]([C:6]1[CH:5]=[C:4]([CH2:13][O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:3]=[C:2]([NH:25][C:24]2[CH:26]=[CH:27][C:28]([N:29]3[CH:33]=[C:32]([CH3:34])[N:31]=[CH:30]3)=[C:22]([O:21][CH3:20])[CH:23]=2)[N:7]=1)=[CH2:9])[CH3:12]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 454801813-methoxy-4-(4-methyl-1H-imidazol-1-yl)anilineHCID 1178207992-Chloro-4-(1-ethoxyvinyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine

Product 1

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

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A vial containing 2-chloro-4-(1-ethoxyvinyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine (0.29 g, 0.98 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.397 g, 1.96 mmol), cesium carbonate (0.637 g, 1.96 mmol), palladium(II) acetate (0.033 g, 0.15 mmol), 2-(dicyclohexylphosphino)biphenyl (0.051 g, 0.15 mmol) and dioxane (14 mL) was capped, evacuated and flushed with nitrogen. The mixture was heated by microwave irradiation at 120° C. for 1.5 h. The volatiles were removed in vacuum and the residue was extracted with ethyl acetate (20 mL). The solution was filtered through a short pad of silica gel, the pad was washed with ethyl acetate and 10% solution of methanol in ethyl acetate. The solvents were removed in vacuum and the residue was purified by column chromatography using a 0-5% gradient of methanol in dichloromethane to yield the title compound, 418 mg (92%).

Workup

  1. customwas capped
  2. customevacuated
  3. customflushed with nitrogen
  4. customThe volatiles were removed in vacuum
  5. extractionthe residue was extracted with ethyl acetate (20 mL)
  6. filtrationThe solution was filtered through a short pad of silica gel
  7. washthe pad was washed with ethyl acetate and 10% solution of methanol in ethyl acetate
  8. customThe solvents were removed in vacuum
  9. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-26f6988d5b824001b38b7b1b7e2773d8
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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