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 2239142Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2239142
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

Komponenten

7

Edukt 4

HCID 7520ThioanisoleHCID 13097Triphenylphosphine Oxide2×HCID 67749Trifluoromethanesulfonic anhydride2×HCID 59303523N-[2-(benzylthio)-3-(1,1-dioxidothiomorpholino)propyl]-5-(2-methoxyethoxy)-7-[(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxamide

Produkt 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-sulfonamideAusbeute 45,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel3×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-b8e2f491ffb14141a8479b6dd1f5f55e
Quelldatensatz
uspto-grants-2010_05
Patentnummer
US07718798B2

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