1-Hydroxybenzotriazole → HCID 86606851, compound

HRID 1442440Notes

Reaction equation

HRID 1442440 reaction equation
[C:1]([C:4]([NH:7][C:8]([CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][C:21]2[C:22]([O:29][C@@H:30]3[O:56][C@H:55]([CH2:57][O:58][C:59](=[O:64])[C:60]([CH3:63])([CH3:62])[CH3:61])[C@@H:47]([O:48][C:49](=[O:54])[C:50]([CH3:53])([CH3:52])[CH3:51])[C@H:39]([O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43])[C@H:31]3[O:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])=[N:23][NH:24][C:25]=2[CH:26]([CH3:28])[CH3:27])=[C:16]([CH3:65])[CH:15]=1)=[O:9])([CH3:6])[CH3:5])(O)=[O:2].[CH2:66]([O:73][C:74]([N:76]1[CH2:81][CH2:80][NH:79][CH2:78][CH2:77]1)=[O:75])[C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.O.C(N(CC)CC)C>[CH2:66]([O:73][C:74]([N:76]1[CH2:81][CH2:80][N:79]([C:1]([C:4]([NH:7][C:8]([CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][C:21]3[C:22]([O:29][C@@H:30]4[O:56][C@H:55]([CH2:57][O:58][C:59](=[O:64])[C:60]([CH3:63])([CH3:62])[CH3:61])[C@@H:47]([O:48][C:49](=[O:54])[C:50]([CH3:53])([CH3:52])[CH3:51])[C@H:39]([O:40][C:41](=[O:46])[C:42]([CH3:43])([CH3:44])[CH3:45])[C@H:31]4[O:32][C:33](=[O:38])[C:34]([CH3:35])([CH3:36])[CH3:37])=[N:23][NH:24][C:25]=3[CH:26]([CH3:27])[CH3:28])=[C:16]([CH3:65])[CH:15]=2)=[O:9])([CH3:5])[CH3:6])=[O:2])[CH2:78][CH2:77]1)=[O:75])[C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 643495Benzyl piperazine-1-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86606852HCID 86606852, compound

Product 1

HCID 86606851HCID 86606851, compoundYield 95.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 4-[(4-{3-[1-carboxy-1-(methyl)ethyl-carbamoyl]propoxy}-2-methylphenyl)methyl]-5-isopropyl-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-pyrazole (0.12 g) in N,N-dimethylformamide (3 mL) were added 1-(benzyloxycarbonyl)piperazine (43 mg), 1-hydroxybenzo-triazole (19 mg), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (50 mg) and triethylamine (0.027 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water. The precipitated crystals were collected by filtration, and washed with water and dried under reduced pressure to give 4-[(4-{3-[1-{[4-(benzyloxycarbonyl)piperazin-1-yl]carbonyl}-1-(methyl)-ethylcarbamoyl]propoxy}-2-methylphenyl)methyl]-5-isopropyl-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-pyrazole (0.14 g). This material was dissolved in ethanol (4 mL). To the solution was added 10% palladium-carbon powder (30 mg), and the mixture was stirred at room temperature under a hydrogen atmosphere for 1.5 hours. The insoluble material was removed by filtration, and the solvent of the filtrate was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=10/1-5/1) to give 5-isopropyl-4-{[4-(3-{1-[(piperazin-1-yl)carbonyl]-1-(methyl)ethylcarbamoyl}propoxy)-2-methyl-phenyl]methyl}-3-(2,3,4,6-tetra-O-pivaloyl-β-D-gluco-pyranosyloxy)-1H-pyrazole (89 mg). This material was dissolved in methanol (6 mL). To the solution was added sodium methoxide (28% methanol solution, 0.087 mL), and the mixture was stirred at 50° C. for 3 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by solid phase extraction on ODS (washing solvent: distilled water, eluent: methanol) to give the title compound (54 mg).

Workup

  1. filtrationThe precipitated crystals were collected by filtration
  2. washwashed with water
  3. customdried under reduced pressure

Sources & evidence

ORD record
ord-61aca6df401e405c84cc513f89a3501b
Source dataset
uspto-grants-2010_02
Patent number
US07655632B2

Reaction notes

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