Ethyl Acetate → (3,5-Bis-trifluoromethyl-benzyl)-[2-(2,4-dimethoxy-pyrimidin-5-yl)-5-trifluoromethyl-benzyl]-[5-(2-methanesulfonyl-ethoxy)-pyrimidin-2-yl]-amine

HRID 604129Notes

Reaction equation

HRID 604129 reaction equation
[F:1][C:2]([F:48])([F:47])[C:3]1[CH:4]=[C:5]([CH:40]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:42]=1)[CH2:6][N:7]([CH2:21][C:22]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:23]=1OS(C(F)(F)F)(=O)=O)[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][S:17]([CH3:20])(=[O:19])=[O:18])=[CH:10][N:9]=1.[CH3:49][O:50][C:51]1[N:56]=[C:55]([O:57][CH3:58])[C:54](B(O)O)=[CH:53][N:52]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(OCC)(=O)C>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].O>[F:46][C:43]([F:45])([F:44])[C:41]1[CH:40]=[C:5]([CH:4]=[C:3]([C:2]([F:48])([F:1])[F:47])[CH:42]=1)[CH2:6][N:7]([CH2:21][C:22]1[CH:27]=[C:26]([C:28]([F:30])([F:29])[F:31])[CH:25]=[CH:24][C:23]=1[C:54]1[C:55]([O:57][CH3:58])=[N:56][C:51]([O:50][CH3:49])=[N:52][CH:53]=1)[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][S:17]([CH3:20])(=[O:18])=[O:19])=[CH:12][N:13]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 2736209(2,4-Dimethoxypyrimidin-5-yl)boronic acidHCID 86626876HCID 86626876, compound

Product 1

HCID 23641905(3,5-Bis-trifluoromethyl-benzyl)-[2-(2,4-dimethoxy-pyrimidin-5-yl)-5-trifluoromethyl-benzyl]-[5-(2-methanesulfonyl-ethoxy)-pyrimidin-2-yl]-amineYield 31.3%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 12976736Bis(ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane);iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Trifluoromethanesulfonic acid 2-({(3,5-bis-trifluoromethyl-benzyl)-[5-(2-methanesulfonyl-ethoxy)-pyrimidin-2-yl]-amino}-methyl)-4-trifluoromethyl-phenyl ester (110 mg) is dissolved in 1,4-dioxane (2 ml) and thereto are added 2,4-dimethoxy-pyrimidine-5-boronic acid (70 mg), palladium acetate (13.2 mg), 1,1′-bis(di-tert-butylphosphino)ferrocene (28 mg) and tripotassium phosphate (62 mg) and the mixture is stirred under nitrogen atmosphere at 80° C. for 4 hours. The reaction solution is cooled to room temperature, and thereto are added ethyl acetate and water, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to give (3,5-bis-trifluoromethyl-benzyl)-[2-(2,4-dimethoxy-pyrimidin-5-yl)-5-trifluoromethyl-benzyl]-[5-(2-methanesulfonyl-ethoxy)-pyrimidin-2-yl]-amine (34 mg). MS (m/z): 740 [M+H]+

Workup

  1. temperatureThe reaction solution is cooled to room temperature
  2. customthe mixture is separated
  3. washthe organic layer is washed with a saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-538a2c96f2ee456c9c0416d251ecf1f9
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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