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 1515719노트

반응식

HRID 1515719 반응식
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]

참가 물질

8

반응물 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

생성물 1

HCID 672286871-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 ester수율 60%

시약·촉매·용매 2

HCID 178477754HCID 178477754, 화합물촉매HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
80 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-9bb9c7d3738c4ad29d45830c00458233
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08222416B2

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