Hydrochloric Acid → 4-(2-{4-[({2-[(3-{[(2-{[(Carboxymethoxy)carbonyl](methyl)amino}ethyl)(pentan-3-yl)amino]methyl}benzoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophen-3-yl}carbonyl)amino]phenyl}ethyl)benzoic acid hydrochloride

HRID 2176043Notes

Reaction equation

HRID 2176043 reaction equation
[CH3:1][N:2]([CH2:11][CH2:12][N:13]([CH:54]([CH2:57][CH3:58])[CH2:55][CH3:56])[CH2:14][C:15]1[CH:16]=[C:17]([CH:51]=[CH:52][CH:53]=1)[C:18]([NH:20][C:21]1[S:22][C:23]2[CH2:50][CH2:49][CH2:48][CH2:47][C:24]=2[C:25]=1[C:26]([NH:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][C:37]2[CH:46]=[CH:45][C:40]([C:41]([O:43]C)=[O:42])=[CH:39][CH:38]=2)=[CH:31][CH:30]=1)=[O:27])=[O:19])[C:3](=[O:10])[O:4][CH2:5][C:6](=[O:9])[O:7]C.CO.[OH-].[Na+].[ClH:63]>C1COCC1>[ClH:63].[C:6]([CH2:5][O:4][C:3]([N:2]([CH3:1])[CH2:11][CH2:12][N:13]([CH2:14][C:15]1[CH:16]=[C:17]([CH:51]=[CH:52][CH:53]=1)[C:18]([NH:20][C:21]1[S:22][C:23]2[CH2:50][CH2:49][CH2:48][CH2:47][C:24]=2[C:25]=1[C:26]([NH:28][C:29]1[CH:30]=[CH:31][C:32]([CH2:35][CH2:36][C:37]2[CH:38]=[CH:39][C:40]([C:41]([OH:43])=[O:42])=[CH:45][CH:46]=2)=[CH:33][CH:34]=1)=[O:27])=[O:19])[CH:54]([CH2:55][CH3:56])[CH2:57][CH3:58])=[O:10])([OH:9])=[O:7]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 90370367Methyl 4-{2-[4-({[2-({3-[7-methyl-3,6-dioxo-10-(pentan-3-yl)-2,5-dioxa-7,10-diazaundecan-11-yl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoate

Product 1

HCID 903702444-(2-{4-[({2-[(3-{[(2-{[(Carboxymethoxy)carbonyl](methyl)amino}ethyl)(pentan-3-yl)amino]methyl}benzoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophen-3-yl}carbonyl)amino]phenyl}ethyl)benzoic acid hydrochloride

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 203 mg of methyl 4-{2-[4-({[2-({3-[7-methyl-3,6-dioxo-10-(pentan-3-yl)-2,5-dioxa-7,10-diazaundecan-11-yl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoate, 4.0 mL of methanol and 4.0 mL of THF was added 1.5 mL of a 1.0 M aqueous sodium hydroxide solution at room temperature, followed by stirring for 14 hours at 60° C. 1.5 mL of 1.0 M hydrochloric acid was added to the reaction mixture under ice cooling, followed by concentration under reduced pressure. A mixed solvent (methanol/chloroform=15/85) was added to the residue, the insoluble material was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (15% methanol/chloroform). A mixed solvent (acetonitrile/water=90/10) was added to the obtained product, 0.5 mL of 1.0 M hydrochloric acid was added thereto under ice cooling, and the solvent was removed under reduced pressure. The residue was subjected to lyophilization, thereby obtaining 186 mg of 4-(2-{4-[({2-[(3-{[(2-{[(carboxymethoxy)carbonyl](methyl)amino}ethyl)(pentan-3-yl)amino]methyl}benzoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophen-3-yl}carbonyl)amino]phenyl}ethyl)benzoic acid hydrochloride.

Workup

  1. concentrationfollowed by concentration under reduced pressure
  2. additionA mixed solvent (methanol/chloroform=15/85) was added to the residue
  3. filtrationthe insoluble material was filtered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (15% methanol/chloroform)
  6. additionA mixed solvent (acetonitrile/water=90/10) was added to the obtained product, 0.5 mL of 1.0 M hydrochloric acid
  7. additionwas added
  8. customunder ice cooling, and the solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-63d67c3fc6aa4b19bd904957b7c95271
Source dataset
uspto-grants-2015_06
Patent number
US09062032B2

Reaction notes

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