Ethyl Acetate → HCID 86626855, compound

HRID 604106Notes

Reaction equation

HRID 604106 reaction equation
[F:1][C:2]([F:51])([F:50])[C:3]1[CH:4]=[C:5]([CH:43]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:45]=1)[CH2:6][N:7]([CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1B1OC(C)(C)C(C)(C)O1)[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:10][N:9]=1.Br[C:53]1[CH:58]=[C:57]([CH3:59])[CH:56]=[CH:55][N:54]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>O1CCOCC1.O>[F:49][C:46]([F:47])([F:48])[C:44]1[CH:43]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:50])[F:51])[CH:45]=1)[CH2:6][N:7]([CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[C:53]1[CH:58]=[C:57]([CH3:59])[CH:56]=[CH:55][N:54]=1)[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12][N:13]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 27340872-Bromo-4-methylpyridineHCID 86626856HCID 86626856, compound

Product 1

HCID 86626855HCID 86626855, compoundYield 44.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl 4-(2-{(3,5-bis-trifluoromethyl-benzyl)-[2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yloxy)-butyrate (200 mg) is dissolved in 1,4-dioxane (4 ml) and thereto are added 2-bromo-4-methyl-pyridine (70 mg), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (22 mg) and cesium carbonate (133 mg), and the mixture is stirred under nitrogen atmosphere at 80° C. for 5 days. 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 NH-silica gel column chromatography (hexane:ethyl acetate=19:1→14:1) to give ethyl 4-(2-{(3,5-bis-trifluoromethyl-benzyl)-[2-(4-methyl-pyridin-2-yl)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yloxy)-butyrate (85 mg). MS (m/z): 701 [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 NH-silica gel column chromatography (hexane:ethyl acetate=19:1→14:1)

Sources & evidence

ORD record
ord-048d959b7dc54f1d91cf8716dba06563
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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