Thioanisole → N-{5-(3-methoxypropoxy)-2-[5-(thiomorpholinomethyl)-4,5-dihydro-1,3-thiazol-2-yl]-1H-indol-7-yl}-N-methylpyridine-2-sulfonamide

HRID 1995014Notes

Reaction equation

HRID 1995014 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]([CH2:75][N:76]1[CH2:81][CH2:80][S:79][CH2:78][CH2:77]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][CH2:61][O:62][CH3:63])=[CH:53][C:52]=2[N:64]([CH3:74])[S:65]([C:68]1[CH:73]=[CH:72][CH:71]=[CH:70][N:69]=1)(=[O:67])=[O:66])=O)C1C=CC=CC=1.C1(SC)C=CC=CC=1.C(=O)([O-])O.[Na+]>C(#N)C>[CH3:63][O:62][CH2:61][CH2:60][CH2:59][O:58][C:54]1[CH:55]=[C:56]2[C:51](=[C:52]([N:64]([CH3:74])[S:65]([C:68]3[CH:73]=[CH:72][CH:71]=[CH:70][N:69]=3)(=[O:67])=[O:66])[CH:53]=1)[NH:50][C:49]([C:47]1[S:43][CH:44]([CH2:75][N:76]3[CH2:81][CH2:80][S:79][CH2:78][CH2:77]3)[CH2:45][N:46]=1)=[CH:57]2

Participants

7

Reactant 5

HCID 7520ThioanisoleHCID 13097Triphenylphosphine OxideHCID 67749Trifluoromethanesulfonic anhydrideHCID 516892Sodium BicarbonateHCID 59303522N-[2-(benzylthio)-3-thiomorpholinopropyl]-5-(3-methoxypropoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxamide

Product 1

HCID 59303548N-{5-(3-methoxypropoxy)-2-[5-(thiomorpholinomethyl)-4,5-dihydro-1,3-thiazol-2-yl]-1H-indol-7-yl}-N-methylpyridine-2-sulfonamideYield 34.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
2.5 °C

Procedure

To a mixture of triphenylphosphine oxide (610 mg) and acetonitrile (10 mL) was added trifluoromethanesulfonic anhydride (310 mg) at 2° C., and the mixture was stirred at 0-5° C. for 30 min. A solution of N-[2-(benzylthio)-3-thiomorpholinopropyl]-5-(3-methoxypropoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxamide (380 mg) and thioanisole (140 mg) in acetonitrile (10 mL) was added dropwise to the reaction mixture at 0-5° C., and the mixture was stirred at 0-5° C. for 30 min. The reaction mixture was poured into saturated aqueous sodium hydrogencarbonate, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was extracted with concentrated hydrochloric acid (10 mL×3), and the hydrochloric acid layers were combined, and washed with ethyl acetate. The aqueous layer was basified with potassium carbonate, and 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 (9:1-1:2, volume ratio) to give the title compound (110 mg, yield 34%) as a colorless oil.

Workup

  1. stirringthe mixture was stirred at 0-5° C. for 30 min
  2. extractionthe mixture was extracted with ethyl acetate
  3. extractionThe ethyl acetate layer was extracted with concentrated hydrochloric acid (10 mL×3)
  4. washwashed with ethyl acetate
  5. extractionextracted 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 (9:1-1:2, volume ratio)

Sources & evidence

ORD record
ord-83341e6698f84f008700385e239142ce
Source dataset
uspto-grants-2010_01
Patent number
US07652133B2

Reaction notes

Loading…