1-(2-Hydroxyethyl)piperazine → HCID 87364130, compound

HRID 2223978Notes

Reaction equation

[C:1]([C:4]([NH:7][C:8]([CH2:10][CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][C:21]2[CH:29]=[CH:28][CH:27]=[C:26]3[C:22]=2[C:23]([O:39][C@@H:40]2[O:66][C@H:65]([CH2:67][O:68][C:69](=[O:74])[C:70]([CH3:73])([CH3:72])[CH3:71])[C@@H:57]([O:58][C:59](=[O:64])[C:60]([CH3:63])([CH3:62])[CH3:61])[C@H:49]([O:50][C:51](=[O:56])[C:52]([CH3:55])([CH3:54])[CH3:53])[C@H:41]2[O:42][C:43](=[O:48])[C:44]([CH3:47])([CH3:46])[CH3:45])=[N:24][N:25]3[CH2:30][CH2:31][O:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:15][CH:14]=1)=[O:9])([CH3:6])[CH3:5])(O)=[O:2].[OH:75][CH2:76][CH2:77][N:78]1[CH2:83][CH2:82][NH:81][CH2:80][CH2:79]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.O.C(N(CC)CC)C>[OH:75][CH2:76][CH2:77][N:78]1[CH2:83][CH2:82][N:81]([C:1]([C:4]([NH:7][C:8]([CH2:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][C:21]3[CH:29]=[CH:28][CH:27]=[C:26]4[C:22]=3[C:23]([O:39][C@@H:40]3[O:66][C@H:65]([CH2:67][O:68][C:69](=[O:74])[C:70]([CH3:73])([CH3:72])[CH3:71])[C@@H:57]([O:58][C:59](=[O:64])[C:60]([CH3:63])([CH3:62])[CH3:61])[C@H:49]([O:50][C:51](=[O:56])[C:52]([CH3:53])([CH3:54])[CH3:55])[C@H:41]3[O:42][C:43](=[O:48])[C:44]([CH3:45])([CH3:46])[CH3:47])=[N:24][N:25]4[CH2:30][CH2:31][O:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:15][CH:14]=2)=[O:9])([CH3:5])[CH3:6])=[O:2])[CH2:80][CH2:79]1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 4-[2-(4-{3-[1-carboxy-1-(methyl)ethyl-carbamoyl]propyl}phenyl)ethyl]-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1-(2-pivaloyloxyethyl)-1H-indazole (40 mg) in N,N-dimethylformamide (1 mL) were added 1-(2-hydroxyethyl)piperazine (6 mg), 1-hydroxybenzotriazole (6 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (11 mg) and triethylamine (0.016 mL), and the mixture was stirred at 50° C. overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water, a saturated aqueous sodium hydrogen carbonate solution and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=10/1-8/1) to give 4-[2-(4-{3-[1-{[4-(2-hydroxyethyl)-piperazin-1-yl]carbonyl}-1-(methyl)ethylcarbamoyl]propyl}-phenyl)ethyl]-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosy loxy)-1-(2-pivaloyloxyethyl)-1H-indazole (22 mg). This material was dissolved in methanol (2 mL). To the solution was added lithium hydroxide monohydrate (8 mg), and the mixture was stirred at room temperature overnight. To the reaction mixture was added acetic acid (0.1 mL), and the resulting mixture was concentrated under reduced pressure. To the residue was added a saturated aqueous potassium carbonate solution, and the mixture was purified by solid phase extraction on ODS (washing solvent: distilled water, eluent:methanol) to give the title compound (11 mg).

Workup

extractionthe resulting mixture was extracted with ethyl acetate
washThe extract was washed with water
dry with materiala saturated aqueous sodium hydrogen carbonate solution and brine, and dried over anhydrous sodium sulfate
customThe solvent was removed under reduced pressure
customthe residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=10/1-8/1)

Sources & evidence

ORD record: ord-bab661c6ea6d4315a77d9952d15ad15c
Source dataset: uspto-grants-2008_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07375113B2

Reaction notes

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