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Sodium Carbonate → 1-benzenesulfonyl-2-(2-cyclopentyl-1-{3-fluoro-4-[1-methyl-1-(tetrahydro-pyran-2-yloxy)-ethyl]-phenyl}-vinyl)-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester

HRID 1515719
Notes
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Reaction equation

HRID 1515719 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:17])([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH3:9])=[C:4]([F:18])[CH:3]=1.C([O-])(=O)C.[K+].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.[CH3:42][O:43][C:44]([C:46]1[CH:47]=[C:48]2[CH:54]=[C:53]([C:55](OS(C3C=CC(C)=CC=3)(=O)=O)=[CH:56][CH:57]3[CH2:61][CH2:60][CH2:59][CH2:58]3)[N:52]([S:73]([C:76]3[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=3)(=[O:75])=[O:74])[C:49]2=[N:50][CH:51]=1)=[O:45].C(=O)([O-])[O-].[Na+].[Na+]>CS(C)=O.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[CH3:42][O:43][C:44]([C:46]1[CH:47]=[C:48]2[CH:54]=[C:53]([C:55]([C:2]3[CH:7]=[CH:6][C:5]([C:8]([CH3:17])([O:10][CH:11]4[CH2:16][CH2:15][CH2:14][CH2:13][O:12]4)[CH3:9])=[C:4]([F:18])[CH:3]=3)=[CH:56][CH:57]3[CH2:58][CH2:59][CH2:60][CH2:61]3)[N:52]([S:73]([C:76]3[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=3)(=[O:74])=[O:75])[C:49]2=[N:50][CH:51]=1)=[O:45]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 672276522-[1-(4-Bromo-2-fluoro-phenyl)-1-methyl-ethoxy]-tetrahydro-pyranHCID 866544971-benzenesulfonyl-2-[2-cyclopentyl-1-(toluene-4-sulfonyloxy)-vinyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester

Product 1

HCID 67228687
1-benzenesulfonyl-2-(2-cyclopentyl-1-{3-fluoro-4-[1-methyl-1-(tetrahydro-pyran-2-yloxy)-ethyl]-phenyl}-vinyl)-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester
Yield 60%

Reagents, catalysts & solvents 2

HCID 178477754HCID 178477754, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 2-[1-(4-bromo-2-fluoro-phenyl)-1-methyl-ethoxy]-tetrahydro-pyran (9.7 g, 30.6 mmol), potassium acetate (9 g, 91.8 mmol) and bis(pinacolato)diboron (9.7 g, 38.2 mmol) in dimethylsulfoxide (65 mL) was added 1,1-bis(diphenylphosphino)ferrocenedichloropalladium(II) (2.5 g, 3.06 mmol) at room temperature. The mixture was heated at 80° C. and stirred for 3 h and then cooled to room temperature and then 1-benzenesulfonyl-2-[2-cyclopentyl-1-(toluene-4-sulfonyloxy)-vinyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester (prepared as in Example 3, 9 g, 15.52 mmol) and an aqueous sodium carbonate solution (2 M, 17.85 mL) were added. The mixture was heated at 100° C. and stirred for 3 h. The resulting mixture was cooled to room temperature, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (QingDao silica gel, 200-300 mesh, 20% ethyl acetate/hexanes) to afford 1-benzenesulfonyl-2-(2-cyclopentyl-1-{3-fluoro-4-[1-methyl-1-(tetrahydro-pyran-2-yloxy)-ethyl]-phenyl}-vinyl)-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester (6 g, 60%) as a light yellow oil: LC/MS m/e calcd for C36H39FN2O6S [M+H]+ 647.78, observed 647.0.

Workup

  1. temperaturecooled to room temperature
  2. temperatureThe mixture was heated at 100° C.
  3. stirringstirred for 3 h
  4. temperatureThe resulting mixture was cooled to room temperature
  5. extractionextracted with ethyl acetate
  6. washwashed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated in vacuo
  9. customthe residue was purified by flash column chromatography (QingDao silica gel, 200-300 mesh, 20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9bb9c7d3738c4ad29d45830c00458233
Source dataset
uspto-grants-2012_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08222416B2

Reaction notes

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