Dimethylformamide → 3-(4-(N-((dimethylamino)methylene)sulfamoyl)phenyl)-N-methoxy-5-(4-methoxyphenyl)-N,4-dimethylthiophene-2-carboxamide

HRID 1518691Notes

Reaction equation

HRID 1518691 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[S:19][C:18]([C:20](O)=[O:21])=[C:17]([C:23]3[CH:28]=[CH:27][C:26]([S:29](=[O:32])(=[O:31])[NH2:30])=[CH:25][CH:24]=3)[C:16]=2[CH3:33])=[CH:11][CH:10]=1.[CH3:34][N:35]([CH:37]=O)[CH3:36].C(N(CC)CC)C.Cl.[CH3:47][NH:48][O:49][CH3:50]>ClCCl>[CH3:37][N:35]([CH:34]=[N:30][S:29]([C:26]1[CH:25]=[CH:24][C:23]([C:17]2[C:16]([CH3:33])=[C:15]([C:12]3[CH:11]=[CH:10][C:9]([O:8][CH3:7])=[CH:14][CH:13]=3)[S:19][C:18]=2[C:20]([N:48]([O:49][CH3:50])[CH3:47])=[O:21])=[CH:28][CH:27]=1)(=[O:31])=[O:32])[CH3:36]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 682852325-(4-Methoxyphenyl)-4-methyl-3-(4-sulfamoylphenyl)thiophene-2-carboxylic acid2×

Product 1

HCID 867050253-(4-(N-((dimethylamino)methylene)sulfamoyl)phenyl)-N-methoxy-5-(4-methoxyphenyl)-N,4-dimethylthiophene-2-carboxamideYield 78.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (1.77 g, 1.2 ml, 13.9 mmol) was added drop wise at 0° C. to a solution of 5-(4-methoxyphenyl)-4-methyl-3-(4-sulfamoylphenyl)thiophene-2-carboxylic acid (compound 7e, 2.8 g, 6.94 mmol) in a mixture of dichloromethane (75 ml) and DMF (1.01 g, 1.1 ml, 13.89 mmol). The so obtained mixture was allowed to come at room temperature and stirred for 1.5 hr under a nitrogen atmosphere. The progress of the reaction was monitored by TLC. The reaction mixture was then concentrated under reduced pressure. The residue so obtained was dissolved in dry dichloromethane (75 ml) and to this was added triethylamine (2.8 g, 3.9 ml, 27.76 mmol) followed by the addition of N,O-dimethylhydroxylamine hydrochloride (1.35 g, 13.89 mmol) under stirring. The reaction mixture was then stirred at room temperature for 2 hr. The progress of the reaction was monitored by TLC. The reaction mixture was then washed with water (2×25 ml) and the organic layer so obtained was dried over anhydrous sodium sulphate and concentrated under reduced pressure to obtain crude product. The crude product was further purified by column chromatography over silica gel (100-200 mesh) using 80% ethyl acetate in hexane as an eluent to obtain the title compound (2.73 g, 78%).

Workup

  1. customThe so obtained mixture
  2. customto come at room temperature
  3. concentrationThe reaction mixture was then concentrated under reduced pressure
  4. customThe residue so obtained
  5. stirringunder stirring
  6. stirringThe reaction mixture was then stirred at room temperature for 2 hr
  7. washThe reaction mixture was then washed with water (2×25 ml)
  8. customthe organic layer so obtained
  9. dry with materialwas dried over anhydrous sodium sulphate
  10. concentrationconcentrated under reduced pressure
  11. customto obtain crude product
  12. customThe crude product was further purified by column chromatography over silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-20ebe1f652e84d9bb454e1d1dbb6db04
Source dataset
uspto-grants-2015_07
Patent number
US09072731B2

Reaction notes

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