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 1994973Notes

Reaction equation

HRID 1994973 reaction equation
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

Participants

7

Reactant 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

Product 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-sulfonamideYield 45.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-d8b610e5cdb147f3b5a22a2a7e2bae6d
Source dataset
uspto-grants-2010_01
Patent number
US07652133B2

Reaction notes

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