Cesium fluoride → HCID 178461600、化合物

HRID 522815ノート

反応式

HRID 522815 の反応式
Cl[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])(=O)C.[K+].Br[C:55]1[NH:56][C:57]2[C:62]([N:63]=1)=[C:61]([N:64]1[CH2:69][CH2:68][O:67][CH2:66][C@H:65]1[CH3:70])[N:60]=[C:59]([N:71]1[CH2:76][CH2:75][O:74][CH2:73][C@@H:72]1[CH3:77])[N:58]=2.[F-].[Cs+]>O1CCOCC1.CCOC(C)=O>[F:11][C:9]1[CH:8]=[C:7]2[C:3]([CH:4]=[CH:5][NH:6]2)=[C:2]([C:55]2[NH:56][C:57]3[C:62]([N:63]=2)=[C:61]([N:64]2[CH2:69][CH2:68][O:67][CH2:66][C@H:65]2[CH3:70])[N:60]=[C:59]([N:71]2[CH2:76][CH2:75][O:74][CH2:73][C@@H:72]2[CH3:77])[N:58]=3)[CH:10]=1

参加物

9

反応物 6

HCID 25953Cesium fluorideHCID 75806TricyclohexylphosphineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 247281774-chloro-6-fluoro-1H-indoleHCID 178461599HCID 178461599、化合物

生成物 1

HCID 178461600HCID 178461600、化合物収率 52.1%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒2 回HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

4-Chloro-6-fluoro-1H-indole (72 mg, 0.42 mmol) was dissolved in 4 mL of dioxane under argon. Bis(pinacolato)diboron (198 mg, 778 μmol), tricyclohexylphospine (19.8 mg, 71 μmol), bis(dibenzylidenacetone)palladium (20.3 mg, 35 μmol), and potassium acetate (104 mg, 1.06 mmol) were added under argon. The reaction was stirred for 24 hours at 80° C. The reaction mixture was cooled to room temperature and diluted with 30 mL of EtOAc. The organic layer was washed with 20 mL of brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was filtered through a column (40 g SiO2; EtOAc/heptane in a gradient from 0/100 to 12/88) to yield a mixture, which was concentrated under reduced pressure, and then dissolved in 2 mL of acetonitrile and 0.2 mL of water under argon. 8-Bromo-2-((S)-3-methylmorpholin-4-yl-)-6-((R)-3-methyl-morpholin-4-yl)-9H-purine (100 mg, 153 μmol) was added, followed by cesium fluoride (25.8 mg, 170 μmol) and tetrakis(triphenylphospine)palladium (26 mg, 23 μmol). The reaction mixture was stirred at 135° C. for 2 hours in a sealed vial. The reaction mixture was cooled to room temperature and diluted with 40 mL of EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (10 g SiO2; tertbutylmethylether) to give the title compound as a foam (36 mg, 19% over 2 steps).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washThe organic layer was washed with 20 mL of brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. filtrationThe residue was filtered through a column (40 g SiO2
  7. customEtOAc/heptane in a gradient from 0/100 to 12/88) to yield a mixture, which
  8. concentrationwas concentrated under reduced pressure
  9. dissolutiondissolved in 2 mL of acetonitrile
  10. stirringThe reaction mixture was stirred at 135° C. for 2 hours in a sealed vial
  11. temperatureThe reaction mixture was cooled to room temperature
  12. washThe organic layer was washed with brine
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe residue was purified by column chromatography (10 g SiO2; tertbutylmethylether)

出典と根拠

ORDレコード
ord-39fcc2fd6f284e548ab0415ad92aa2e5
出典データセット
uspto-grants-2016_05
特許番号
US09334271B2

反応ノート

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