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

HRID 709742Notes

Reaction equation

HRID 709742 reaction equation
Cl[C:2]1[C:7]([F:8])=[C:6]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[CH:19][C:18]=3[F:25])=[C:13]([CH2:26][C:27]([CH3:30])([CH3:29])[CH3:28])[N:12]=2)[N:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([CH:39]=[CH:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])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>[CH3:28][C:27]([CH3:30])([CH3:29])[CH2:26][C:13]1[N:12]=[C:11]([CH2:10][O:9][C:6]2[N:5]=[CH:4][N:3]=[C:2](/[CH:39]=[CH:40]/[C:41]([O:43][CH2:44][CH3:45])=[O:42])[C:7]=2[F:8])[CH:16]=[CH:15][C:14]=1[C:17]1[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[CH:19][C:18]=1[F:25]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 54570828HCID 54570828, compoundHCID 1177602054-Chloro-6-((6-(2,2-dimethylpropyl)-5-(2-fluoro-5-methoxyphenyl)pyridin-2-yl)methoxy)-5-fluoropyrimidine

Product 1

HCID 131733913ethyl (2E)-3-(6-((6-(2,2-dimethylpropyl)-5-(2-fluoro-5-methoxyphenyl)pyridin-2-yl)methoxy)-5-fluoropyrimidin-4-yl)acrylateYield 26.7%

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-fluoropyrimidine (930 mg) in DMF (10 mL) were added ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (970 mg), tris(dibenzylideneacetone)dipalladium (250 mg), cesium carbonate (1.00 g) and dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (205 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 (285 mg) 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-93d37a3310bc4313b6246b84d8e7bf98
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

Loading…