Sulfuric Acid → N-[2-[5-(hydroxymethyl)-4,5-dihydro-1,3-thiazol-2-yl]-5-(2-methoxyethoxy)-1H-indol-7-yl]-N,1-dimethyl-1H-imidazole-2-sulfonamide

HRID 2239176Notes

Reaction equation

HRID 2239176 reaction equation
C[O:2][CH:3](OC)[CH:4]1[S:8][C:7]([C:9]2[NH:10][C:11]3[C:16]([CH:17]=2)=[CH:15][C:14]([O:18][CH2:19][CH2:20][O:21][CH3:22])=[CH:13][C:12]=3[N:23]([CH3:33])[S:24]([C:27]2[N:28]([CH3:32])[CH:29]=[CH:30][N:31]=2)(=[O:26])=[O:25])=[N:6][CH2:5]1.FC(F)(F)C(O)=O.S(=O)(=O)(O)O.[BH4-].[Na+]>O1CCCC1.C(O)C.O>[OH:2][CH2:3][CH:4]1[S:8][C:7]([C:9]2[NH:10][C:11]3[C:16]([CH:17]=2)=[CH:15][C:14]([O:18][CH2:19][CH2:20][O:21][CH3:22])=[CH:13][C:12]=3[N:23]([CH3:33])[S:24]([C:27]2[N:28]([CH3:32])[CH:29]=[CH:30][N:31]=2)(=[O:25])=[O:26])=[N:6][CH2:5]1

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 6422Trifluoroacetic acidHCID 4311764Sodium borohydrideHCID 59135952HCID 59135952, compound

Product 1

HCID 59136141N-[2-[5-(hydroxymethyl)-4,5-dihydro-1,3-thiazol-2-yl]-5-(2-methoxyethoxy)-1H-indol-7-yl]-N,1-dimethyl-1H-imidazole-2-sulfonamideYield 10%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of N-[2-[5-(dimethoxymethyl)-4,5-dihydro-1,3-thiazol-2-yl]-5-(2-methoxyethoxy)-1H-indol-7-yl]-N,1-dimethyl-1H-imidazole-2-sulfonamide (335 mg), trifluoroacetic acid (4 mL) and water (12 mL) was added concentrated sulfuric acid (4 mL), and the mixture was stirred at 60° C. for 2 hr. The excess trifluoroacetic acid was evaporated under reduced pressure, and the residue was neutralized with sodium hydrogencarbonate. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and filtrated, and the filtrate was concentrated under reduced pressure. The obtained crude product was dissolved in a mixed solvent of tetrahydrofuran (3 mL) and ethanol (2 mL), and sodium borohydride (26.5 mg) was added under ice-cooling. The reaction solution was stirred at room temperature for 2 hr, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with 1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over magnesium sulfate, and filtrated, and the filtrate was concentrated under reduced pressure. The residue was silica gel column chromatography (ethyl acetate:hexane=20:80-90:10), and the obtained crude product was further purified by preparative HPLC to give the title compound (30.8 mg, yield 10%) as a white solid.

Workup

  1. customThe excess trifluoroacetic acid was evaporated under reduced pressure
  2. extractionThe reaction mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltrated
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe obtained crude product
  8. additionwas added under ice-
  9. temperaturecooling
  10. stirringThe reaction solution was stirred at room temperature for 2 hr
  11. extractionthe mixture was extracted with ethyl acetate
  12. washThe organic layer was washed successively with 1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine
  13. dry with materialdried over magnesium sulfate
  14. filtrationfiltrated
  15. concentrationthe filtrate was concentrated under reduced pressure
  16. customthe obtained crude product
  17. customwas further purified by preparative HPLC

Sources & evidence

ORD record
ord-dd9ae767c96d4540b79f809969805fb4
Source dataset
uspto-grants-2010_05
Patent number
US07718798B2

Reaction notes

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