Cesium carbonate → 4-(1-Ethoxyvinyl)-N-(3-methoxy-4-(2-methyloxazol-5-yl)phenyl)-6-((2,2,2-trifluoroethoxy)-methyl)pyrimidin-2-amine

HRID 59121Notes

Reaction equation

HRID 59121 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[C:29]1[O: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>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[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]([C:29]3[O: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 686321593-Methoxy-4-(2-methyloxazol-5-yl)benzenamineHCID 1178207992-Chloro-4-(1-ethoxyvinyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine

Product 1

HCID 1178211374-(1-Ethoxyvinyl)-N-(3-methoxy-4-(2-methyloxazol-5-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

2-Chloro-4-(1-ethoxyvinyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine (0.10 g, 0.34 mmol) was dissolved in dioxane (5 mL). 3-Methoxy-4-(2-methyloxazol-5-yl)aniline (0.069 g, 0.34 mmol), cesium carbonate (0.220 g, 0.67 mmol), palladium(II) acetate (0.011 g, 0.05 mmol) and 2-(dicyclohexylphosphino)biphenyl (0.018 g, 0.05 mmol) were added. The vial was capped, evacuated and flushed with nitrogen. The mixture was heated by microwave irradiation at 120° C. for 1.5 h. The solvents were evaporated. EtOAc was added and the mixture was filtered through a plug of silica. The solvents were evaporated and the residue was purified by column chromatography on silica eluting with EtAOc to give the title compound as a solid, 138 mg (88%).

Workup

  1. customThe vial was capped
  2. customevacuated
  3. customflushed with nitrogen
  4. customThe solvents were evaporated
  5. additionEtOAc was added
  6. filtrationthe mixture was filtered through a plug of silica
  7. customThe solvents were evaporated
  8. customthe residue was purified by column chromatography on silica eluting with EtAOc

Sources & evidence

ORD record
ord-277baf025f194474993e4fcea85753a3
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

Loading…