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Methanol → N-[2-chloro-4-[[[(1H-indazol-4-yl)methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine, methyl ester

HRID 1352075
Notes
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Reaction equation

HRID 1352075 reaction equation
[Cl:1][C:2]1[CH:23]=[C:22]([C:24]([NH:26][CH2:27][C:28]2[CH:36]=[CH:35][CH:34]=[C:33]3[C:29]=2[CH:30]=[N:31][N:32]3C2CCCCO2)=[O:25])[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][C@H:7]([C:17]([OH:19])=[O:18])[CH2:8][NH:9][C:10]([C:12]1[S:13][CH:14]=[CH:15][CH:16]=1)=[O:11])=[O:5].[CH3:43]O>Cl>[Cl:1][C:2]1[CH:23]=[C:22]([C:24]([NH:26][CH2:27][C:28]2[CH:36]=[CH:35][CH:34]=[C:33]3[C:29]=2[CH:30]=[N:31][NH:32]3)=[O:25])[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][C@H:7]([C:17]([OH:19])=[O:18])[CH2:8][NH:9][C:10]([C:12]1[S:13][CH:14]=[CH:15][CH:16]=1)=[O:11])=[O:5].[Cl:1][C:2]1[CH:23]=[C:22]([C:24]([NH:26][CH2:27][C:28]2[CH:36]=[CH:35][CH:34]=[C:33]3[C:29]=2[CH:30]=[N:31][NH:32]3)=[O:25])[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][C@H:7]([C:17]([O:19][CH3:43])=[O:18])[CH2:8][NH:9][C:10]([C:12]1[S:13][CH:14]=[CH:15][CH:16]=1)=[O:11])=[O:5]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 887MethanolHCID 68821073N-[2-chloro-4-[[[[1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl]methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine

Product 2

HCID 59977260N-[2-chloro-4-[[[(1H-indazol-4-yl)methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanineYield 26%HCID 131723037N-[2-chloro-4-[[[(1H-indazol-4-yl)methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine, methyl ester
Yield 42%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A solution of N-[2-chloro-4-[[[[1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl]methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine (35 mg, 0.057 mmol) in 2 M HCl (2 mL) and methanol (2 mL) was heated at reflux for 3 h. The solution was concentrated, diluted with aqueous acetic acid and purified by HPLC to give N-[2-chloro-4-[[[(1H-indazol-4-yl)methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine (8 mg, 26%) along with N-[2-chloro-4-[[[(1H-indazol-4-yl)methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine, methyl ester (13 mg, 42%).

Workup

  1. temperatureat reflux for 3 h
  2. concentrationThe solution was concentrated
  3. additiondiluted with aqueous acetic acid
  4. custompurified by HPLC

Sources & evidence

ORD record
ord-c7fd83c9b6be4a7a84c2db194d34d8e0
Source dataset
uspto-grants-2007_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07217728B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes