Sodium Hydroxide → HCID 178524340, compound

HRID 926056Notes

Reaction equation

HRID 926056 reaction equation
[CH:1]1([N:4]([CH:47]2[CH2:52][CH2:51][CH:50]([C:53]([O:55]CC)=[O:54])[CH2:49][CH2:48]2)[S:5]([C:8]2[CH:9]=[C:10]([CH:44]=[CH:45][CH:46]=2)[C:11]([NH:13][C:14]2[S:15][C:16]3[CH2:43][CH2:42][CH2:41][CH2:40][C:17]=3[C:18]=2[C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][C:30]3[CH:39]=[CH:38][C:33]([C:34]([O:36]C)=[O:35])=[CH:32][CH:31]=3)=[CH:24][CH:23]=2)=[O:20])=[O:12])(=[O:7])=[O:6])[CH2:3][CH2:2]1.[OH-].[Na+]>C(O)C>[C:53]([C@H:50]1[CH2:51][CH2:52][C@H:47]([N:4]([CH:1]2[CH2:2][CH2:3]2)[S:5]([C:8]2[CH:9]=[C:10]([CH:44]=[CH:45][CH:46]=2)[C:11]([NH:13][C:14]2[S:15][C:16]3[CH2:43][CH2:42][CH2:41][CH2:40][C:17]=3[C:18]=2[C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][C:30]3[CH:31]=[CH:32][C:33]([C:34]([OH:36])=[O:35])=[CH:38][CH:39]=3)=[CH:24][CH:23]=2)=[O:20])=[O:12])(=[O:6])=[O:7])[CH2:48][CH2:49]1)([OH:55])=[O:54].[C:53]([C@@H:50]1[CH2:51][CH2:52][C@H:47]([N:4]([CH:1]2[CH2:2][CH2:3]2)[S:5]([C:8]2[CH:9]=[C:10]([CH:44]=[CH:45][CH:46]=2)[C:11]([NH:13][C:14]2[S:15][C:16]3[CH2:43][CH2:42][CH2:41][CH2:40][C:17]=3[C:18]=2[C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][C:30]3[CH:31]=[CH:32][C:33]([C:34]([OH:36])=[O:35])=[CH:38][CH:39]=3)=[CH:24][CH:23]=2)=[O:20])=[O:12])(=[O:6])=[O:7])[CH2:48][CH2:49]1)([OH:55])=[O:54]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 71238590Methyl 4-(2-{4-[({2-[(3-{cyclopropyl[4-(ethoxycarbonyl)cyclohexyl]sulfamoyl}benzoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophen-3-yl}carbonyl)amino]phenyl}ethyl)benzoate

Product 2

HCID 178524340HCID 178524340, compoundHCID 178524341HCID 178524341, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 300 mg of methyl 4-(2-{4-[({2-[(3-{cyclopropyl[4-(ethoxycarbonyl)cyclohexyl]sulfamoyl}benzoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophen-3-yl}carbonyl)amino]phenyl}ethyl)benzoate, 1.0 mL of a 1.0 M aqueous sodium hydroxide solution, and 3.0 mL of ethanol was heated and refluxed for 3 days. The reaction mixture was concentrated under reduced pressure and the residue was neutralized with 1.0 M hydrochloric acid, and then the precipitate was collected by filtration. The obtained solid was purified by silica gel column chromatography (chloroform-methanol) to obtain 4-{2-[4-({[2-({3-[(trans-4-carboxycyclohexyl)(cyclopropyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoic acid (high polarity product) and 4-{2-[4-({[2-({3-[(cis-4-carboxycyclohexyl)(cyclopropyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoic acid (low polarity product). The products were each suspended in ethyl acetate-hexane to obtain 114 mg of 4-{2-[4-({[2-({3-[(trans-4-carboxycyclohexyl)(cyclopropyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoic acid (Example 4) and 56 mg of 4-{2-[4-({[2-({3-[(cis-4-carboxycyclohexyl)(cyclopropyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoic acid (Example 5), respectively, as colorless crystals.

Workup

  1. temperaturewas heated
  2. temperaturerefluxed for 3 days
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. filtrationthe precipitate was collected by filtration
  5. customThe obtained solid was purified by silica gel column chromatography (chloroform-methanol)

Sources & evidence

ORD record
ord-3b77c30a120d4ffd8416471ff4887433
Source dataset
uspto-grants-2016_03
Patent number
US09284295B2

Reaction notes

Loading…