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

HRID 59164Notes

Reaction equation

HRID 59164 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][C:9]=1[N:10]1[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11]1)[NH2:6].Cl[C:17]1[N:22]=[C:21]([NH:23][CH2:24][C:25]([CH3:28])([OH:27])[CH3:26])[CH:20]=[C:19]([CH2:29][O:30][CH2:31][C:32]([F:35])([F:34])[F:33])[N:18]=1.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>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:6][C:17]2[N:22]=[C:21]([NH:23][CH2:24][C:25]([CH3:26])([OH:27])[CH3:28])[CH:20]=[C:19]([CH2:29][O:30][CH2:31][C:32]([F:35])([F:33])[F:34])[N:18]=2)[CH:7]=[CH:8][C:9]=1[N:10]1[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11]1

Participants

7

Reactant 4

HCID 10796Cesium carbonate2×HCID 27342162-(Dicyclohexylphosphino)biphenyl2×HCID 454801813-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline2×HCID 1178210421-(2-Chloro-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-ylamino)-2-methylpropan-2-ol

Product 1

HCID 863453381-(2-(3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)-methyl)pyrimidin-4-ylamino)-2-methylpropan-2-olYield 30.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (45 mg, 0.22 mmol), 1-(2-chloro-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-ylamino)-2-methylpropan-2-ol (35 mg, 0.11 mmol), cesium carbonate (73 mg, 0.22 mmol), palladium(II) acetate (4 mg, 0.02 mmol) and 2-(dicyclohexylphosphino)biphenyl (6 mg, 0.02 mmol) in dioxane (1 mL) was heated at 120° C. by microwave irradiation under nitrogen atmosphere for 90 minutes. An additional equivalent of each: 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline, cesium carbonate, palladium(II) acetate and 2-(dicyclohexylphosphino)biphenyl was added and the reaction mixture was heated by microwave irradiation at 120° C. for additional 90 minutes. The mixture was filtered and purified by preparative HPLC to give the title compound as a solid 16 mg (29%).

Workup

  1. temperaturethe reaction mixture was heated by microwave irradiation at 120° C. for additional 90 minutes
  2. filtrationThe mixture was filtered
  3. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-5bcdf91ba95740e790b733e9f92eb2b9
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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