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1-Hydroxybenzotriazole → 3-methoxymethyl-1-{2-oxo-2-[4-(4-pyrimidin-2-yl-phenyl)-piperazin-1-yl]-ethyl}-pyrrolidine-3-carboxylic acid [3-(4-fluoro-phenyl)-1H-indazol-5-yl]-amide

HRID 1038023
Notes
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Reaction equation

HRID 1038023 reaction equation
[CH3:1][O:2][CH2:3][C:4]1([C:30](O)=[O:31])[CH2:8][CH2:7][N:6]([CH2:9][C:10](=[O:29])[N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]4[N:28]=[CH:27][CH:26]=[CH:25][N:24]=4)=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)[CH2:5]1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[F:55][C:56]1[CH:61]=[CH:60][C:59]([C:62]2[C:70]3[C:65](=[CH:66][CH:67]=[C:68]([NH2:71])[CH:69]=3)[NH:64][N:63]=2)=[CH:58][CH:57]=1>CN(C=O)C>[F:55][C:56]1[CH:57]=[CH:58][C:59]([C:62]2[C:70]3[C:65](=[CH:66][CH:67]=[C:68]([NH:71][C:30]([C:4]4([CH2:3][O:2][CH3:1])[CH2:8][CH2:7][N:6]([CH2:9][C:10](=[O:29])[N:11]5[CH2:12][CH2:13][N:14]([C:17]6[CH:18]=[CH:19][C:20]([C:23]7[N:28]=[CH:27][CH:26]=[CH:25][N:24]=7)=[CH:21][CH:22]=6)[CH2:15][CH2:16]5)[CH2:5]4)=[O:31])[CH:69]=3)[NH:64][N:63]=2)=[CH:60][CH:61]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 224802843-(4-fluorophenyl)-1H-indazol-5-amineHCID 595113503-Methoxymethyl-1-{2-oxo-2-[4-(4-pyrimidin-2-yl-phenyl)-piperazin-1-yl]-ethyl}-pyrrolidine-3-carboxylic acid

Product 1

HCID 57685735
3-methoxymethyl-1-{2-oxo-2-[4-(4-pyrimidin-2-yl-phenyl)-piperazin-1-yl]-ethyl}-pyrrolidine-3-carboxylic acid [3-(4-fluoro-phenyl)-1H-indazol-5-yl]-amide
Yield 28.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The 3-methoxymethyl-1-{2-oxo-2-[4-(4-pyrimidin-2-yl-phenyl)-piperazin-1-yl]-ethyl}-pyrrolidine-3-carboxylic acid (0.049 mmol), 1-hydroxybenztriazole (7 mg, 0.052 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCl) (10 mg, 0.052 mmol) were dissolved in dry DMF (1 ml). 3-(4-Fluoro-phenyl)-1H-indazol-5-ylamine (12 mg, 0.053 mmol) was added and the reaction mixture was stirred overnight and directly subjected to purification by reversed phase HPLC to obtain 9.15 mg of the title product.

Workup

  1. customdirectly subjected to purification by reversed phase HPLC

Sources & evidence

ORD record
ord-02d269ca453145a3806bca47bd98e79d
Source dataset
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08546404B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes