Cesium carbonate → ethyl (2E)-3-(6-((6-(2,2-dimethylpropyl)-5-(2-fluoro-5-methoxyphenyl)pyridin-2-yl)methoxy)-5-methoxypyrimidin-4-yl)acrylate

HRID 709739Notes

Reaction equation

HRID 709739 reaction equation
Cl[C:2]1[C:7]([O:8][CH3:9])=[C:6]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:19]=3[F:26])=[C:14]([CH2:27][C:28]([CH3:31])([CH3:30])[CH3:29])[N:13]=2)[N:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([CH:40]=[CH:41][C:42]([O:44][CH2:45][CH3:46])=[O:43])O1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>CN(C=O)C.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>[CH3:29][C:28]([CH3:31])([CH3:30])[CH2:27][C:14]1[N:13]=[C:12]([CH2:11][O:10][C:6]2[N:5]=[CH:4][N:3]=[C:2](/[CH:40]=[CH:41]/[C:42]([O:44][CH2:45][CH3:46])=[O:43])[C:7]=2[O:8][CH3:9])[CH:17]=[CH:16][C:15]=1[C:18]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:19]=1[F:26]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 54570828HCID 54570828, compoundHCID 1177602634-Chloro-6-((6-(2,2-dimethylpropyl)-5-(2-fluoro-5-methoxyphenyl)pyridin-2-yl)methoxy)-5-methoxypyrimidine

Product 1

HCID 131733912ethyl (2E)-3-(6-((6-(2,2-dimethylpropyl)-5-(2-fluoro-5-methoxyphenyl)pyridin-2-yl)methoxy)-5-methoxypyrimidin-4-yl)acrylateYield 79.5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-chloro-6-((6-(2,2-dimethylpropyl)-5-(2-fluoro-5-methoxyphenyl)pyridin-2-yl)methoxy)-5-methoxypyrimidine (1.20 g) in DMF (10 mL) were added ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (1.22 g), tris(dibenzylideneacetone)dipalladium (310 mg), cesium carbonate (1.30 g) and dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (257 mg), and the mixture was stirred at 90° C. for 6 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (1.09 g) as a white solid.

Workup

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

Sources & evidence

ORD record
ord-712ca55f26734b5ca8efe4e61d4f477d
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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