Dimethyl Sulfide → N-methyl-N-[2-[5-(morpholinomethyl)-4,5-dihydro-1,3-thiazol-2-yl]-5-(trifluoromethoxy)-1H-indol-7-yl]thiophene-2-sulfonamide

HRID 1994956Notes

Reaction equation

HRID 1994956 reaction equation
C1(P(=O)(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][O: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][C:59]([F:62])([F:61])[F:60])=[CH:53][C:52]=2[N:63]([CH3:72])[S:64]([C:67]1[S:68][CH:69]=[CH:70][CH:71]=1)(=[O:66])=[O:65])=O)C1C=CC=CC=1.CSC>ClCCl.O>[CH3:72][N:63]([C:52]1[CH:53]=[C:54]([O:58][C:59]([F:62])([F:60])[F:61])[CH:55]=[C:56]2[C:51]=1[NH:50][C:49]([C:47]1[S:43][CH:44]([CH2:73][N:74]3[CH2:79][CH2:78][O:77][CH2:76][CH2:75]3)[CH2:45][N:46]=1)=[CH:57]2)[S:64]([C:67]1[S:68][CH:69]=[CH:70][CH:71]=1)(=[O:65])=[O:66]

Participants

7

Reactant 4

HCID 1068Dimethyl SulfideHCID 13097Triphenylphosphine OxideHCID 67749Trifluoromethanesulfonic anhydrideHCID 59135860HCID 59135860, compound

Product 1

HCID 59135761N-methyl-N-[2-[5-(morpholinomethyl)-4,5-dihydro-1,3-thiazol-2-yl]-5-(trifluoromethoxy)-1H-indol-7-yl]thiophene-2-sulfonamideYield 44.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of triphenylphosphine oxide (670 mg) in dichloromethane (15 mL) was added trifluoromethanesulfonic anhydride (340 mg) under ice-cooling, and the mixture was stirred for 10 min. A solution of N-[2-(benzylthio)-3-morpholinopropyl]-7-[methyl(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxamide (400 mg) and dimethylsulfide (40 mg) in dichloromethane (15 mL) was added dropwise to the reaction mixture under ice-cooling, and the mixture was stirred for 2 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 basic silica gel column chromatography, and eluted with hexane-ethyl acetate (4:1-2:1, volume ratio). The obtained compound was further purified by preparative HPLC to give the title compound (150 mg, yield 44%) as white crystals. The crystals were recrystallized from ethyl acetate-hexane to give colorless prism crystals. melting point 165-166° C.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringthe mixture was stirred for 2 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 (4:1-2:1, volume ratio)
  10. customThe obtained compound was further purified by preparative HPLC

Sources & evidence

ORD record
ord-dc0eade0bb114edfb2fd6104180cfbca
Source dataset
uspto-grants-2010_01
Patent number
US07652133B2

Reaction notes

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