Dimethyl Sulfide → N-{2-[5-(1,4-dioxa-8-azaspiro[4.5]dec-8-ylmethyl)-5-methyl-4,5-dihydro-1,3-thiazol-2-yl]-1H-indol-7-yl}-N-methylthiophene-2-sulfonamide

HRID 1960456Notes

Reaction equation

HRID 1960456 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][C:44]([CH3:79])([CH2:68][N:69]1[CH2:78][CH2:77][C:72]2([O:76][CH2:75][CH2:74][O:73]2)[CH2:71][CH2:70]1)[CH2:45][NH:46][C:47]([C:49]1[NH:50][C:51]2[C:56]([CH:57]=1)=[CH:55][CH:54]=[CH:53][C:52]=2[N:58]([CH3:67])[S:59]([C:62]1[S:63][CH:64]=[CH:65][CH:66]=1)(=[O:61])=[O:60])=O)C1C=CC=CC=1.CSC.C(=O)([O-])O.[Na+]>ClCCl>[O:73]1[C:72]2([CH2:77][CH2:78][N:69]([CH2:68][C:44]3([CH3:79])[S:43][C:47]([C:49]4[NH:50][C:51]5[C:56]([CH:57]=4)=[CH:55][CH:54]=[CH:53][C:52]=5[N:58]([CH3:67])[S:59]([C:62]4[S:63][CH:64]=[CH:65][CH:66]=4)(=[O:60])=[O:61])=[N:46][CH2:45]3)[CH2:70][CH2:71]2)[O:76][CH2:75][CH2:74]1

Participants

7

Reactant 5

HCID 1068Dimethyl SulfideHCID 13097Triphenylphosphine OxideHCID 67749Trifluoromethanesulfonic anhydrideHCID 516892Sodium BicarbonateHCID 59135582HCID 59135582, compound

Product 1

HCID 59135738N-{2-[5-(1,4-dioxa-8-azaspiro[4.5]dec-8-ylmethyl)-5-methyl-4,5-dihydro-1,3-thiazol-2-yl]-1H-indol-7-yl}-N-methylthiophene-2-sulfonamideYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of triphenylphosphine oxide (0.83 g) in dichloromethane (6 mL) was slowly added trifluoromethanesulfonic anhydride (0.25 mL) at 0° C., and the mixture was added for 10 min. N-[2-(benzylthio)-3-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-2-methylpropyl]-7-[methyl(2-thienylsulfonyl)amino]-1H-indole-2-carboxamide (0.72 g) and dimethylsulfide (0.22 mL) were added, and the reaction mixture was stirred at 0° C. for 20 min. Saturated aqueous sodium hydrogencarbonate was added, 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 from a fraction eluted with ethyl acetate-hexane (2:3, volume ratio) to give the title compound (0.28 g, yield 50%) as colorless crystals. melting point 172-173° C.

Workup

  1. customat 0° C.
  2. additionthe mixture was added for 10 min
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with saturated brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. washeluted with ethyl acetate-hexane (2:3, volume ratio)

Sources & evidence

ORD record
ord-04c25ce51d7b4a978396806bd1601906
Source dataset
uspto-grants-2013_04
Patent number
US08410087B2

Reaction notes

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