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

HRID 59100Notes

Reaction equation

HRID 59100 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]([O:34][CH3:35])[N:31]=[CH:30]1)[NH2:25].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>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]([O:34][CH3:35])[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 1178207992-Chloro-4-(1-ethoxyvinyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidineHCID 1178238413-methoxy-4-(4-methoxy-1H-imidazol-1-yl)aniline

Product 1

HCID 1178240104-(1-Ethoxyvinyl)-N-(3-methoxy-4-(4-methoxy-1H-imidazol-1-yl)phenyl)-6-((2,2,2-trifluoro-ethoxy)methyl)pyrimidin-2-amine

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

2-Chloro-4-(1-ethoxyvinyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine (0.230 g, 0.78 mmol), 3-methoxy-4-(4-methoxy-1H-imidazol-1-yl)aniline, palladium(II) acetate (0.026 g, 0.12 mmol), 2-(dicyclohexylphosphino)biphenyl (0.041 g, 0.12 mmol), cesium carbonate (0.505 g, 1.55 mmol) and dioxane (20 mL) were mixed in a vial. The vial was capped, evacuated and flushed with nitrogen. The mixture was heated by microwave irradiation at 120° C. for 1.5 h. The mixture was filtrated through pad of silica and silica was washed by EtOAc containing 10% of MeOH. The solvents were evaporated and the residue was purified by column chromatography eluting with gradient of MeOH and DCM to give the title compound as a dry film, 0.313 g (84%).

Workup

  1. customThe vial was capped
  2. customevacuated
  3. customflushed with nitrogen
  4. filtrationThe mixture was filtrated through pad of silica and silica
  5. washwas washed by EtOAc containing 10% of MeOH
  6. customThe solvents were evaporated
  7. customthe residue was purified by column chromatography
  8. washeluting with gradient of MeOH and DCM

Sources & evidence

ORD record
ord-cdc05590ab414a0f910d3c4cf75610a3
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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