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 2239054Notes

Reaction equation

HRID 2239054 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-952051669b364e1ca0f8832524eef09f
Source dataset
uspto-grants-2010_05
Patent number
US07718798B2

Reaction notes

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