Chloroform → HCID 86626861, compound

HRID 604111Notes

Reaction equation

HRID 604111 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.Cl[C:53]1[C:58]([O:59][CH3:60])=[CH:57][N:56]=[C:55]([S:61][CH3:62])[N:54]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)(Cl)Cl>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[C:58]([O:59][CH3:60])=[CH:57][N:56]=[C:55]([S:61][CH3:62])[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 6212ChloroformHCID 10796Cesium carbonateHCID 2435114-Chloro-5-methoxy-2-(methylsulfanyl)pyrimidineHCID 86626856HCID 86626856, compound

Product 1

HCID 86626861HCID 86626861, compoundYield 53%

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 (300 mg) is dissolved in 1,4-dioxane (5 ml) and thereto are added 4-chloro-5-methoxy-2-methylsulfanyl-pyrimidine (117 mg), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (33 mg) and cesium carbonate (199 mg), and the mixture is stirred under nitrogen atmosphere at 80° C. overnight. The reaction solution is cooled to room temperature, and thereto are added chloroform and water, and the insoluble materials are removed by filtration through Celite™. The filtrate is separated, and the organic layer is dried and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=9:1→7:3) to give ethyl 4-(2-{(3,5-bis-trifluoromethyl-benzyl)-[2-(5-methoxy-2-methylsulfanyl-pyrimidin-4-yl)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yloxy)-butyrate (165 mg). MS (m/z): 764 [M+H]+

Workup

  1. temperatureThe reaction solution is cooled to room temperature
  2. customthe insoluble materials are removed by filtration through Celite™
  3. customThe filtrate is separated
  4. customthe organic layer is dried
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=9:1→7:3)

Sources & evidence

ORD record
ord-869fe35485dd4c19bbb310b3feafa4cc
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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