Cesium carbonate → Methyl 4-((1-(4-(5-chloropyrimidin-2-yl)-2-methylphenyl)-4,4,4-trifluorobutyl)amino)benzoate

HRID 1520251Notes

Reaction equation

HRID 1520251 reaction equation
[F:1][C:2]([F:34])([F:33])[CH2:3][CH2:4][CH:5]([NH:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=1)[C:6]1[CH:11]=[CH:10][C:9](B2OC(C)(C)C(C)(C)O2)=[CH:8][C:7]=1[CH3:21].[Cl:35][C:36]1[CH:37]=[N:38][C:39](I)=[N:40][CH:41]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl-].[NH4+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.CN(C)C=O>[Cl:35][C:36]1[CH:37]=[N:38][C:39]([C:9]2[CH:10]=[CH:11][C:6]([CH:5]([NH:22][C:23]3[CH:24]=[CH:25][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:31][CH:32]=3)[CH2:4][CH2:3][C:2]([F:34])([F:33])[F:1])=[C:7]([CH3:21])[CH:8]=2)=[N:40][CH:41]=1

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 299380055-Chloro-2-iodopyrimidineHCID 131733097Methyl 4-((4,4,4-trifluoro-1-(2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)butyl)amino)benzoate

Product 1

HCID 117840298Methyl 4-((1-(4-(5-chloropyrimidin-2-yl)-2-methylphenyl)-4,4,4-trifluorobutyl)amino)benzoateYield 60.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A reaction mixture of methyl 4-((4,4,4-trifluoro-1-(2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)butyl)amino)benzoate (7.85 g) obtained in Example 1, step F, 5-chloro-2-iodopyrimidine (4.35 g), tris(dibenzylideneacetone)dipalladium (0.753 g), 2,6-dimethoxy-2′-(dicyclohexylphosphino)biphenyl (1.35 g), cesium carbonate (16.08 g), dimethylformamide (65.8 mL) and water (16.5 ml) was stirred at 60° C. for 24 hr under a nitrogen atmosphere. The reaction mixture was added to saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (hexane/ethyl acetate) and washed with diethyl ether to give the title compound (4.61 g).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
  6. washwashed with diethyl ether

Sources & evidence

ORD record
ord-849b768d54b14d16bb20768b42f6484e
Source dataset
uspto-grants-2015_07
Patent number
US09073864B2

Reaction notes

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