Thioanisole → N-[2-(1,8-dithia-3-azaspiro[4.5]dec-2-en-2-yl)-5-(2-methoxyethoxy)-1H-indol-7-yl]-N-methylpyridine-2-sulfonamide

HRID 1960451Notes

Reaction equation

HRID 1960451 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]1([CH2:50][NH:51][C:52]([C:54]2[NH:55][C:56]3[C:61]([CH:62]=2)=[CH:60][C:59]([O:63][CH2:64][CH2:65][O:66][CH3:67])=[CH:58][C:57]=3[N:68]([CH3:78])[S:69]([C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][N:73]=2)(=[O:71])=[O:70])=O)[CH2:49][CH2:48][S:47][CH2:46][CH2:45]1)C1C=CC=CC=1.C1(SC)C=CC=CC=1.C(=O)([O-])O.[Na+]>C(#N)C>[S:43]1[C:44]2([CH2:49][CH2:48][S:47][CH2:46][CH2:45]2)[CH2:50][N:51]=[C:52]1[C:54]1[NH:55][C:56]2[C:61]([CH:62]=1)=[CH:60][C:59]([O:63][CH2:64][CH2:65][O:66][CH3:67])=[CH:58][C:57]=2[N:68]([CH3:78])[S:69]([C:72]1[CH:77]=[CH:76][CH:75]=[CH:74][N:73]=1)(=[O:70])=[O:71]

Participants

7

Reactant 5

HCID 7520ThioanisoleHCID 13097Triphenylphosphine OxideHCID 67749Trifluoromethanesulfonic anhydrideHCID 516892Sodium BicarbonateHCID 59135936N-{[4-(benzylthio)tetrahydro-2H-thiopyran-4-yl]methyl)-5-(2-methoxyethoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxamide

Product 1

HCID 59135931N-[2-(1,8-dithia-3-azaspiro[4.5]dec-2-en-2-yl)-5-(2-methoxyethoxy)-1H-indol-7-yl]-N-methylpyridine-2-sulfonamideYield 17%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of triphenylphosphine oxide (2.0 g) in acetonitrile (14 mL) was added dropwise trifluoromethanesulfonic anhydride (1.0 mL) at 0° C., and the mixture was stirred at 0° C. for 30 min. The obtained suspension was diluted with acetonitrile (36 mL), and a solution of N-{[4-(benzylthio)tetrahydro-2H-thiopyran-4-yl]methyl}-5-(2-methoxyethoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxamide (1.9 g) and thioanisole (0.70 mL) in acetonitrile (50 mL) was added. The reaction mixture was stirred at 0° C. for 2 hr, saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, dried (MgSO4), and concentrated. The obtained residue was subjected to silica gel column chromatography, and eluted with hexane-ethyl acetate (9:1-3:7, volume ratio) to give the title compound (0.26 g, yield 17%) as colorless crystals.

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 2 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with water and saturated brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. washeluted with hexane-ethyl acetate (9:1-3:7, volume ratio)

Sources & evidence

ORD record
ord-77258aeacef0434fa3b896b58982ba3e
Source dataset
uspto-grants-2013_04
Patent number
US08410087B2

Reaction notes

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