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

HRID 1995016Notes

Reaction equation

HRID 1995016 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]([CH3:81])([CH2:74][N:75]1[CH2:80][CH2:79][S:78][CH2:77][CH2:76]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][O:61][CH3:62])=[CH:53][C:52]=2[N:63]([CH3:73])[S:64]([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][N:68]=1)(=[O:66])=[O:65])=O)C1C=CC=CC=1.C1(SC)C=CC=CC=1.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:62][O:61][CH2:60][CH2:59][O:58][C:54]1[CH:55]=[C:56]2[C:51](=[C:52]([N:63]([CH3:73])[S:64]([C:67]3[CH:72]=[CH:71][CH:70]=[CH:69][N:68]=3)(=[O:66])=[O:65])[CH:53]=1)[NH:50][C:49]([C:47]1[S:43][C:44]([CH3:81])([CH2:74][N:75]3[CH2:76][CH2:77][S:78][CH2:79][CH2:80]3)[CH2:45][N:46]=1)=[CH:57]2

Participants

7

Reactant 5

HCID 7520ThioanisoleHCID 13097Triphenylphosphine OxideHCID 67749Trifluoromethanesulfonic anhydrideHCID 516892Sodium BicarbonateHCID 59135650N-[2-(benzylthio)-2-methyl-3-thiomorpholinopropyl]-5-(2-methoxyethoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxamide

Product 1

HCID 59135671N-(5-(2-methoxyethoxy)-2-[5-methyl-5-(thiomorpholinomethyl)-4,5-dihydro-1,3-thiazol-2-yl]-1H-indol-7-yl}-N-methylpyridine-2-sulfonamideYield 15.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a mixture of triphenylphosphine oxide (178 mg) and dichloromethane (8 mL) was added trifluoromethanesulfonic anhydride (0.11 mL) at 0° C., the mixture was stirred at 0° C. for 15 min, and dichloromethane (4 mL) was added. A mixture of N-[2-(benzylthio)-2-methyl-3-thiomorpholinopropyl]-5-(2-methoxyethoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxamide (220 mg), thioanisole (0.075 mL) and dichloromethane (3 mL) was added to the reaction solution at −78° C., and the mixture was stirred at −78° C. for 10 min. Aqueous sodium bicarbonate was added, and the mixture was extracted with dichloromethane. The extract was washed with saturated brine, dried over sodium sulfate, and filtrated, and the filtrate was concentrated. The residue was subjected to silica gel column chromatography, and eluted with ethyl acetate. The obtained amorphous solid was purified by preparative HPLC to give the title compound (28 mg, yield 15%) as a colorless amorphous solid.

Workup

  1. additionwas added to the reaction solution at −78° C.
  2. stirringthe mixture was stirred at −78° C. for 10 min
  3. extractionthe mixture was extracted with dichloromethane
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltrated
  7. concentrationthe filtrate was concentrated
  8. washeluted with ethyl acetate
  9. customThe obtained amorphous solid was purified by preparative HPLC

Sources & evidence

ORD record
ord-4e82d0d2a84e4da08ae36209277ad0e5
Source dataset
uspto-grants-2010_01
Patent number
US07652133B2

Reaction notes

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