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

HRID 504917노트

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HRID 504917 반응식
FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([S:43][CH:44]([CH2:73][N:74]1[CH2:79][CH2:78][S:77](=[O:81])(=[O:80])[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>ClCCl.O>[O:80]=[S:77]1(=[O:81])[CH2:76][CH2:75][N:74]([CH2:73][CH:44]2[S:43][C:47]([C:49]3[NH:50][C:51]4[C:56]([CH:57]=3)=[CH:55][C:54]([O:58][CH2:59][CH2:60][O:61][CH3:62])=[CH:53][C:52]=4[NH:63][S:64]([C:67]3[CH:72]=[CH:71][CH:70]=[CH:69][N:68]=3)(=[O:66])=[O:65])=[N:46][CH2:45]2)[CH2:79][CH2:78]1

참가 물질

7

반응물 4

HCID 7520ThioanisoleHCID 13097Triphenylphosphine Oxide2회HCID 67749Trifluoromethanesulfonic anhydride2회HCID 59303523N-[2-(benzylthio)-3-(1,1-dioxidothiomorpholino)propyl]-5-(2-methoxyethoxy)-7-[(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxamide

생성물 1

HCID 67487668N-[2-{5-[(1,1-dioxidothiomorpholino)methyl]-4,5-dihydro-1,3-thiazol-2-yl}-5-(2-methoxyethoxy)-1H-indol-7-yl]pyridine-2-sulfonamide수율 45.2%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매3회

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온도
0 °C

실험 절차

A mixture of trifluoromethanesulfonic anhydride (100 mg), triphenylphosphine oxide (95 mg) and dichloromethane (5 mL) was stirred at 0° C. for 10 min. A solution of N-[2-(benzylthio)-3-(1,1-dioxidothiomorpholino)propyl]-5-(2-methoxyethoxy)-7-[(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxamide (210 mg) and thioanisole (80 mg) in dichloromethane (40 mL) was added dropwise to the reaction mixture under ice-cooling, and the mixture was stirred for 2 hr under ice-cooling. The reaction mixture was added dropwise to a mixture of trifluoromethanesulfonic anhydride (100 mg), triphenylphosphine oxide (95 mg) and dichloromethane (2 mL) under ice-cooling, and the mixture was stirred at room temperature for 15 hr. 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 residue was subjected to silica gel column chromatography, and eluted with hexane-ethyl acetate (2:3-5:95, volume ratio) to give the title compound (80 mg, yield 44%) as colorless crystals. The crystals were recrystallized from acetone-hexane to give colorless prism crystals. melting point 218-219° C.

후처리

  1. temperaturecooling
  2. stirringthe mixture was stirred for 2 hr under ice-
  3. temperaturecooling
  4. temperaturecooling
  5. stirringthe mixture was stirred at room temperature for 15 hr
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe ethyl acetate layer was washed with saturated brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. washeluted with hexane-ethyl acetate (2:3-5:95, volume ratio)

출처 및 근거

ORD 기록
ord-37bd0566348e4c56b03dab969e3f30b9
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07777047B2

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