Cesium carbonate → 1-(2-(3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-yl)-2-methylpropan-1-ol

HRID 59144Notes

Reaction equation

HRID 59144 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH:8]([OH:12])[CH:9]([CH3:11])[CH3:10])[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].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:20][O:21][C:22]1[CH:23]=[C:24]([NH:25][C:2]2[N:7]=[C:6]([CH:8]([OH:12])[CH:9]([CH3:11])[CH3:10])[CH:5]=[C:4]([CH2:13][O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:3]=2)[CH:26]=[CH:27][C:28]=1[N:29]1[CH:33]=[C:32]([CH3:34])[N:31]=[CH:30]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 454801813-methoxy-4-(4-methyl-1H-imidazol-1-yl)anilineHCID 121317230HCID 121317230, compound

Product 1

HCID 863440651-(2-(3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-yl)-2-methylpropan-1-ol

Reagents, catalysts & solvents 2

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

Conditions

Temperature
130 °C

Procedure

1-(2-Chloro-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-yl)-2-methylpropan-1-ol (20 mg, 0.07 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (13.61 mg, 0.07 mmol), palladium(II) acetate (2.255 mg, 10.04 μmol),2-(dicyclohexylphosphino)biphenyl (3.52 mg, 10.04 μmol), and cesium carbonate (43.6 mg, 0.13 mmol) were mixed in dioxane (3 mL). The vial was flushed with nitrogen, capped and heated by microwave irradiation at 130° C. for 2.5 h. The mixture was filtered through a pad of silica gel, the pad was eluted with DCM and 5% MeOH in DCM. The solvents were evaporated. The residue was purified by preparative HPLC to give the title compound as a dry film, 9 mg (27%).

Workup

  1. customThe vial was flushed with nitrogen
  2. customcapped
  3. filtrationThe mixture was filtered through a pad of silica gel
  4. washthe pad was eluted with DCM and 5% MeOH in DCM
  5. customThe solvents were evaporated
  6. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-63ca8b0af1554a11839096bd0866a659
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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