Aminoisobutyric acid → 3-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-4-[(4-{(1E)-2-[1-carboxy-1-(methyl)ethylcarbamoyl]vinyl}phenyl)methyl]-5-isopropyl-1H-pyrazole

HRID 2223618Notes

Reaction equation

HRID 2223618 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](/[CH:37]=[CH:38]/[C:39](O)=[O:40])=[CH:33][CH:32]=2)=[C:28]([CH:42]([CH3:44])[CH3:43])[NH:27][N:26]=1)(=[O:3])[CH3:2].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[NH2:67][C:68]([CH3:73])([CH3:72])[C:69]([OH:71])=[O:70]>CN(C)C=O.ClCCl.O.C(O)(=O)C.C(N(CC)CC)C>[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:32]=[CH:33][C:34](/[CH:37]=[CH:38]/[C:39](=[O:40])[NH:67][C:68]([C:69]([OH:71])=[O:70])([CH3:73])[CH3:72])=[CH:35][CH:36]=2)=[C:28]([CH:42]([CH3:44])[CH3:43])[NH:27][N:26]=1)(=[O:3])[CH3:2]

Participants

10

Reactant 4

HCID 6119Aminoisobutyric acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 685386823-(2,3,4,6-tetra-O-acetyl-beta-D-gluco-pyranosyloxy)-4-({4-[(1E)-2-carboxyvinyl]phenyl}methyl)-5-isopropyl-1H-pyrazole

Product 1

HCID 685359163-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-4-[(4-{(1E)-2-[1-carboxy-1-(methyl)ethylcarbamoyl]vinyl}phenyl)methyl]-5-isopropyl-1H-pyrazoleYield 32.2%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-({4-[(1E)-2-carboxyvinyl]phenyl}methyl)-5-isopropyl-1H-pyrazole (1.2 g) in N,N-dimethylformamide (15 mL) and dichloromethane (10 mL) was added triethylamine (15 mL). To the mixture were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.56 g), 1-hydroxybenzotriazole (0.4 g), and a solution of 2-amino-2-methylpropionic acid (2.0 g) in water (15 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was neutralized by addition of 2 mol/L aqueous acetic acid solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine successively, 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: ethyl acetate-dichloromethane/methanol=7/1-3/1) to give 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-[(4-{(1E)-2-[1-carboxy-1-(methyl)-ethylcarbamoyl]vinyl}phenyl)methyl]-5-isopropyl-1H-pyrazole (0.44 g). This material was dissolved in N,N-dimethylformamide (0.3 mL). To the solution were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.18 g), 1-hydroxybenzotriazole (0.13 g) and N,N-dimethylethylenediamine (0.55 g), and the mixture was stirred at room temperature overnight. To the reaction mixture was added 5 mol/L aqueous sodium hydroxide solution (1.5 mL), and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added acetic acid (1 mL), and the mixture was diluted with water (3 mL). The insoluble material was removed by filtration, and the filtrate was purified by preparative reverse phase column chromatography (Shiseido CAPCELL PAK UG120 ODS, 5 μL, 120 Å, 20×50 mm, flow rate 30 mL/minute linear gradient, water/acetonitrile=90/10-10/60) to give the title compound (71 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and brine successively
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was purified by column chromatography on silica gel (eluent: ethyl acetate-dichloromethane/methanol=7/1-3/1)

Sources & evidence

ORD record
ord-778e21b855d34ec5a9b6f4c37c1b4573
Source dataset
uspto-grants-2008_05
Patent number
US07375087B2

Reaction notes

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