Thioanisole → N-(5-(2-methoxyethoxy)-2-{5-[(1-oxidothiomorpholino)methyl]-4,5-dihydro-1,3-thiazol-2-yl}-1H-indol-7-yl)pyridine-2-sulfonamide

HRID 504918노트

반응식

HRID 504918 반응식
C1(P(=[O:20])(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C([S:43][CH:44]([CH2:73][N:74]1[CH2:79][CH2:78][S:77][CH2:76][CH2:75]1)[CH2:45][NH:46][C:47]([C:49]1[NH:50][C:51]2[C:56]([CH:57]=1)=[CH:55][C:54]([O:58][CH2:59][CH2:60][O:61][CH3:62])=[CH:53][C:52]=2[NH:63][S:64]([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][N:68]=1)(=[O:66])=[O:65])=O)C1C=CC=CC=1.C1(SC)C=CC=CC=1.OOS([O-])=O.[K+].S([O-])([O-])=O.[Na+].[Na+]>ClCCl.O1CCCC1.O.C(O)C>[CH3:62][O:61][CH2:60][CH2:59][O:58][C:54]1[CH:55]=[C:56]2[C:51](=[C:52]([NH:63][S:64]([C:67]3[CH:72]=[CH:71][CH:70]=[CH:69][N:68]=3)(=[O:66])=[O:65])[CH:53]=1)[NH:50][C:49]([C:47]1[S:43][CH:44]([CH2:73][N:74]3[CH2:75][CH2:76][S:77](=[O:20])[CH2:78][CH2:79]3)[CH2:45][N:46]=1)=[CH:57]2

참가 물질

11

반응물 6

HCID 7520ThioanisoleHCID 13097Triphenylphosphine OxideHCID 24437Sodium SulfiteHCID 67749Trifluoromethanesulfonic anhydrideHCID 23707502Potassium hydroxy sulfiteHCID 59303541N-[2-(benzylthio)-3-thiomorpholinopropyl]-5-(2-methoxyethoxy)-7-[(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxamide

생성물 1

HCID 59356796N-(5-(2-methoxyethoxy)-2-{5-[(1-oxidothiomorpholino)methyl]-4,5-dihydro-1,3-thiazol-2-yl}-1H-indol-7-yl)pyridine-2-sulfonamide수율 6.1%

시약·촉매·용매 4

HCID 702Ethanol용매HCID 962Water용매2회HCID 6344Dichloromethane용매2회HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of triphenylphosphine oxide (470 mg) in dichloromethane (3 mL) was added trifluoromethanesulfonic anhydride (480 mg) under ice-cooling, and the mixture was stirred for 30 min. A solution of N-[2-(benzylthio)-3-thiomorpholinopropyl]-5-(2-methoxyethoxy)-7-[(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxamide (570 mg) and thioanisole (210 mg) in dichloromethane (20 mL) was added dropwise to the reaction mixture under ice-cooling, and the mixture was stirred for 3 hr under ice-cooling. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4), and concentrated. The obtained residue was subjected to silica gel column chromatography, and eluted with hexane-ethyl acetate (1:1-1:9, volume ratio) to give colorless crystals. To a mixture of the obtained crystals, ethanol (20 mL), water (10 mL) and tetrahydrofuran (10 mL) was added OXONE (registered trade mark, 43 mg) at room temperature, and the mixture was stirred at room temperature for 2 hr. Aqueous sodium sulfite solution was added to the reaction mixture, the mixture was stirred for 30 min, and the organic solvent was evaporated under reduced pressure. The residue was extracted with a mixed solvent of ethyl acetate-tetrahydrofuran. The organic layer was washed with saturated brine, dried (MgSO4), and concentrated. The residue was subjected to silica gel column chromatography, and eluted with ethyl acetate-methanol (100:0-90:10, volume ratio) to give colorless crystals. The obtained crystals was further purified by preparative HPLC, and recrystallized from acetone-methanol to give the title compound (30 mg, yield 6.1%) as colorless prism crystals. melting point 235-236° C.

후처리

  1. temperaturecooling
  2. temperaturecooling
  3. stirringthe mixture was stirred for 3 hr under ice-
  4. temperaturecooling
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe ethyl acetate layer was washed with saturated brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. washeluted with hexane-ethyl acetate (1:1-1:9, volume ratio)
  10. customto give colorless crystals
  11. stirringthe mixture was stirred at room temperature for 2 hr
  12. stirringthe mixture was stirred for 30 min
  13. customthe organic solvent was evaporated under reduced pressure
  14. extractionThe residue was extracted with a mixed solvent of ethyl acetate-tetrahydrofuran
  15. washThe organic layer was washed with saturated brine
  16. dry with materialdried (MgSO4)
  17. concentrationconcentrated
  18. washeluted with ethyl acetate-methanol (100:0-90:10, volume ratio)
  19. customto give colorless crystals
  20. customThe obtained crystals was further purified by preparative HPLC
  21. customrecrystallized from acetone-methanol

출처 및 근거

ORD 기록
ord-13a16867257543598d2ef93be248b1a5
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07777047B2

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