N-Methylpiperidine → N-methyl-N-methoxy-2-chloro-5-sulfamoylthiophene-3-carboxamide

HRID 1197434Notes

Reaction equation

HRID 1197434 reaction equation
[Cl:1][C:2]1[S:6][C:5]([S:7]([NH2:10])(=[O:9])=[O:8])=[CH:4][C:3]=1[C:11]([OH:13])=O.CN1CCCCC1.Cl.[CH3:22][NH:23][O:24][CH3:25].C([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:22][N:23]([O:24][CH3:25])[C:11]([C:3]1[CH:4]=[C:5]([S:7](=[O:9])(=[O:8])[NH2:10])[S:6][C:2]=1[Cl:1])=[O:13]

Participants

6

Reactant 4

HCID 12291N-MethylpiperidineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 516892Sodium BicarbonateHCID 12014982-Chloro-5-sulfamoylthiophene-3-carboxylic acid

Product 1

HCID 19106478N-methyl-N-methoxy-2-chloro-5-sulfamoylthiophene-3-carboxamideYield 40.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1,1-Carbonyldiimidazole (7.70 g, 0.047 mol) was added portionwise to a solution of 5-chloro-4-carboxythiophene-2-sulfonamide (7.25 g, 0.03 mol) in DMF (60 mL). After two hours, N-methylpiperidine (6.0 mL, 0.05 mol) and N,O-dimethylhydroxylamine hydrochloride (5.2 g, 0.05 mol) were added to the reaction mixture. After an additional four hours at room temperature, the reaction mixture was poured into ice/water saturated with NaHCO3. The crude product was extracted into ethyl acetate, the extract was dried (anhydrous Na2SO4), filtered and evaporated. The crude residue was chromatographed on silica gel and eluted with 59% methanol/methylene chloride to give 3.45 g (40%) of white solid product, mp 223°-225° C.

Workup

  1. waitAfter an additional four hours at room temperature
  2. extractionThe crude product was extracted into ethyl acetate
  3. dry with materialthe extract was dried (anhydrous Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude residue was chromatographed on silica gel
  7. washeluted with 59% methanol/methylene chloride

Sources & evidence

ORD record
ord-1cc4ccf734414bdb81426a48f463ec72
Source dataset
uspto-grants-1994_01
Patent number
US05276025

Reaction notes

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