Sodium Hydroxide → 4-{2-[4-({[2-({3-[(1-Carboxycyclopropyl)(isopropyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoic acid

HRID 1025457Notes

Reaction equation

HRID 1025457 reaction equation
C([O:3][C:4]([C:6]1([N:9]([CH:51]([CH3:53])[CH3:52])[S:10]([C:13]2[CH:14]=[C:15]([CH:48]=[CH:49][CH:50]=2)[C:16]([NH:18][C:19]2[S:20][C:21]3[CH2:47][CH2:46][CH2:45][CH2:44][C:22]=3[C:23]=2[C:24]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([CH2:33][CH2:34][C:35]3[CH:43]=[CH:42][C:38]([C:39]([OH:41])=[O:40])=[CH:37][CH:36]=3)=[CH:29][CH:28]=2)=[O:25])=[O:17])(=[O:12])=[O:11])[CH2:8][CH2:7]1)=[O:5])C.[OH-].[Na+]>C(O)C>[C:4]([C:6]1([N:9]([CH:51]([CH3:53])[CH3:52])[S:10]([C:13]2[CH:14]=[C:15]([CH:48]=[CH:49][CH:50]=2)[C:16]([NH:18][C:19]2[S:20][C:21]3[CH2:47][CH2:46][CH2:45][CH2:44][C:22]=3[C:23]=2[C:24]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([CH2:33][CH2:34][C:35]3[CH:36]=[CH:37][C:38]([C:39]([OH:41])=[O:40])=[CH:42][CH:43]=3)=[CH:29][CH:28]=2)=[O:25])=[O:17])(=[O:12])=[O:11])[CH2:7][CH2:8]1)([OH:5])=[O:3]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 682077874-(2-{4-[({2-[(3-{[1-(Ethoxycarbonyl)cyclopropyl](isopropyl)sulfamoyl}benzoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophen-3-yl}carbonyl)amino]phenyl}ethyl)benzoic acid

Product 1

HCID 545885204-{2-[4-({[2-({3-[(1-Carboxycyclopropyl)(isopropyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoic acidYield 56.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 137 mg of 4-(2-{4-[({2-[(3-{[1-(ethoxycarbonyl)cyclopropyl](isopropyl)sulfamoyl}benzoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophen-3-yl}carbonyl)amino]phenyl}ethyl)benzoic acid, 0.5 mL of a 5.0 M aqueous sodium hydroxide, and 1.4 mL of ethanol was heated and refluxed overnight. The reaction mixture was concentrated under reduced pressure, and to the residue were added water, citric acid, dichloromethane, and THF in this order. The organic layer was separated and then concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform-methanol). The obtained crude product was washed with diethyl ether to obtain 74 mg of 4-{2-[4-({[2-({3-[(1-carboxycyclopropyl)(isopropyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoic acid as a pale yellow crystal.

Workup

  1. temperaturewas heated
  2. temperaturerefluxed overnight
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionto the residue were added water, citric acid, dichloromethane, and THF in this order
  5. customThe organic layer was separated
  6. concentrationconcentrated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (chloroform-methanol)
  8. customThe obtained crude product
  9. washwas washed with diethyl ether

Sources & evidence

ORD record
ord-0489d9fa1de445a8bc729fc71a79988a
Source dataset
uspto-grants-2014_05
Patent number
US08729068B2

Reaction notes

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