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 926068Notes

Reaction equation

HRID 926068 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-27258c785ff44d5491bce346c02b8fda
Source dataset
uspto-grants-2016_03
Patent number
US09284295B2

Reaction notes

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