Dichloromethane → 4-{2-[4-({[2-({3-[(2-Carboxyethyl)(methyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoic acid

HRID 1025450Notes

Reaction equation

HRID 1025450 reaction equation
C([O:5][C:6](=[O:53])[CH2:7][CH2:8][N:9]([CH3:52])[S:10]([C:13]1[CH:14]=[C:15]([CH:49]=[CH:50][CH:51]=1)[C:16]([NH:18][C:19]1[S:20][C:21]2[CH2:48][CH2:47][CH2:46][CH2:45][C:22]=2[C:23]=1[C:24]([NH:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][CH2:34][C:35]2[CH:44]=[CH:43][C:38]([C:39]([O:41]C)=[O:40])=[CH:37][CH:36]=2)=[CH:29][CH:28]=1)=[O:25])=[O:17])(=[O:12])=[O:11])(C)(C)C.FC(F)(F)C(O)=O.ClCCl.[OH-].[Na+]>C(O)C>[C:6]([CH2:7][CH2:8][N:9]([CH3:52])[S:10]([C:13]1[CH:14]=[C:15]([CH:49]=[CH:50][CH:51]=1)[C:16]([NH:18][C:19]1[S:20][C:21]2[CH2:48][CH2:47][CH2:46][CH2:45][C:22]=2[C:23]=1[C:24]([NH:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][CH2:34][C:35]2[CH:36]=[CH:37][C:38]([C:39]([OH:41])=[O:40])=[CH:43][CH:44]=2)=[CH:29][CH:28]=1)=[O:25])=[O:17])(=[O:12])=[O:11])([OH:53])=[O:5]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 71238619Methyl 4-{2-[4-({[2-({3-[(3-tert-butoxy-3-oxopropyl)(methyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoate

Product 1

HCID 682078524-{2-[4-({[2-({3-[(2-Carboxyethyl)(methyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoic acidYield 74.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 200 mg of methyl 4-{2-[4-({[2-({3-[(3-tert-butoxy-3-oxopropyl)(methyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoate, 2.0 mL of trifluoroacetic acid, and 2.0 mL of dichloromethane was stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure, and to the obtained crude product were added 0.50 mL of a 5.0 M aqueous sodium hydroxide solution and 2.0 mL of ethanol, followed by heating and refluxing overnight. The reaction mixture was concentrated under reduced pressure and to the obtained residue were added water and citric acid (500 mg), followed by extraction with dichloromethane. The organic layer was concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography (chloroform-methanol). The crude product was washed with ethyl acetate to obtain 135 mg of 4-{2-[4-({[2-({3-[(2-carboxyethyl)(methyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoic acid as a colorless crystal.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto the obtained crude product
  3. temperatureby heating
  4. temperaturerefluxing overnight
  5. concentrationThe reaction mixture was concentrated under reduced pressure and to the obtained residue
  6. additionwere added water and citric acid (500 mg)
  7. extractionfollowed by extraction with dichloromethane
  8. concentrationThe organic layer was concentrated under reduced pressure
  9. customthe obtained residue was purified by silica gel column chromatography (chloroform-methanol)
  10. washThe crude product was washed with ethyl acetate

Sources & evidence

ORD record
ord-092d1d68139147e889e3c81c1e8b07c6
Source dataset
uspto-grants-2014_05
Patent number
US08729068B2

Reaction notes

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