Water → N-(5-acetyl-2-methyl-4H-thieno[3,2-b]pyrrol-3-yl)-N-methylthiophene-2-sulfonamide

HRID 453595Notes

Reaction equation

HRID 453595 reaction equation
CON(C)[C:4]([C:6]1[NH:10][C:9]2[C:11]([N:15]([CH3:24])[S:16]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)(=[O:18])=[O:17])=[C:12]([CH3:14])[S:13][C:8]=2[CH:7]=1)=[O:5].[H-].[Na+].[CH3:28]OCCl.O>CN(C)C=O>[C:4]([C:6]1[NH:10][C:9]2[C:11]([N:15]([CH3:24])[S:16]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)(=[O:17])=[O:18])=[C:12]([CH3:14])[S:13][C:8]=2[CH:7]=1)(=[O:5])[CH3:28]

Participants

6

Reactant 4

HCID 962WaterHCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 59411392N-methoxy-N,2-dimethyl-3-[methyl(2-thienylsulfonyl)amino]-4H-thieno[3,2-b]pyrrole-5-carboxamide

Product 1

HCID 59411393N-(5-acetyl-2-methyl-4H-thieno[3,2-b]pyrrol-3-yl)-N-methylthiophene-2-sulfonamideYield 27%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-methoxy-N,2-dimethyl-3-[methyl(2-thienylsulfonyl)amino]-4H-thieno[3,2-b]pyrrole-5-carboxamide (230 mg) in N,N-dimethylformamide (5 mL) was added sodium hydride (60%, oily, 25 mg), and the mixture was stirred at room temperature for 30 min. Chloromethyl methyl ether (51 mg) was added to the reaction mixture, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was dissolved in tetrahydrofuran (5 mL), methyl magnesium bromide (ca. 3.0M diethyl ether solution, 0.4 mL) was added thereto, and the mixture was stirred at room temperature for 30 min. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was dissolved in tetrahydrofuran (5 mL), 6N hydrochloric acid (5.0°mL) was added thereto, and the mixture was stirred at 80° C. overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography to give N-(5-acetyl-2-methyl-4H-thieno[3,2-b]pyrrol-3-yl)-N-methylthiophene-2-sulfonamide (55.2 mg, yield 26%) as gray crystals from a fraction eluted with ethyl acetate-hexane (1:1, volume ratio). melting point 220° C.

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with saturated brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  7. additionmethyl magnesium bromide (ca. 3.0M diethyl ether solution, 0.4 mL) was added
  8. stirringthe mixture was stirred at room temperature for 30 min
  9. additionWater was added to the reaction mixture
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe ethyl acetate layer was washed with saturated brine
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated
  14. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  15. addition6N hydrochloric acid (5.0°mL) was added
  16. stirringthe mixture was stirred at 80° C. overnight
  17. additionWater was added to the reaction mixture
  18. extractionthe mixture was extracted with ethyl acetate
  19. washThe ethyl acetate layer was washed with saturated brine
  20. dry with materialdried (MgSO4)
  21. concentrationconcentrated

Sources & evidence

ORD record
ord-4d04889eec2640018d892ac4a8128ffd
Source dataset
uspto-grants-2013_07
Patent number
US08492405B2

Reaction notes

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