3-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-4-{[4-(3-aminopropoxy)-2-methylphenyl]-methyl}-5-isopropyl-1H-pyrazole → HCID 178476367, compound

HRID 2189372Notes

Reaction equation

HRID 2189372 reaction equation
[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][CH2:40][NH2:41])=[CH:33][C:32]=2[CH3:42])=[C:28]([CH:43]([CH3:45])[CH3:44])[NH:27][N:26]=1)(=[O:3])[CH3:2].[CH2:46]([O:53][C:54]([NH:56][C:57](N1C=CC=N1)=[NH:58])=[O:55])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>O1CCCC1>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][CH2:40][NH:41][C:57]([NH2:58])=[N:56][C:54]([O:53][CH2:46][C:47]3[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=3)=[O:55])=[CH:33][C:32]=2[CH3:42])=[C:28]([CH:43]([CH3:45])[CH3:44])[NH:27][N:26]=1)(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 689401203-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-4-{[4-(3-aminopropoxy)-2-methylphenyl]-methyl}-5-isopropyl-1H-pyrazoleHCID 137319688N-(Carbobenzoxy)-1H-pyrazole-1-carboxamidine

Product 1

HCID 178476367HCID 178476367, compoundYield 55.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-{[4-(3-aminopropoxy)-2-methylphenyl]-methyl}-5-isopropyl-1H-pyrazole (70 mg) in tetrahydrofuran (3 mL) was added N-(benzyloxycarbonyl)-1H-pyrazole-1-carboxamidine (0.27 g), and the mixture was stirred at 60° C. for 20 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/1-ethyl acetate-ethyl acetate/ethanol=10/1) to give 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-({4-[3-(N′-benzyloxycarbonylguanidino)propoxy]-2-methylphenyl)methyl}-5-isopropyl-1H-pyrazole (50 mg). This material was dissolved in methanol (1 mL). To the solution was added sodium methoxide (28% methanol solution, 0.01 mL), and the mixture was stirred at room temperature for 1 hour. 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 4-({4-[3-(N′-benzyloxycarbonylguanidino)propoxy]-2-methylphenyl}methyl)-3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazole (35 mg). This material was dissolved in methanol (2 mL). To the solution was added 10% palladium-carbon powder (15 mg), and the mixture was stirred at room temperature under a hydrogen atmosphere for 2 hours. The insoluble material was removed by filtration, and the solvent of the filtrate was removed under reduced pressure to give the title compound (27 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/1-ethyl acetate-ethyl acetate/ethanol=10/1)

Sources & evidence

ORD record
ord-76bd7cbe025e475b8da9e2a39e27d923
Source dataset
uspto-grants-2012_12
Patent number
US08324176B2

Reaction notes

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