1-Hydroxybenzotriazole → 4-({4-[(1E)-3-(carbamoyl-methylcarbamoyl)prop-1-enyl]phenyl}methyl)-3-(beta-D-gluco-pyranosyloxy)-5-isopropyl-1H-pyrazole

HRID 1442370Notes

Reaction equation

HRID 1442370 reaction equation
C([O:4][C@@H:5]1[C@@H:10]([O:11]C(=O)C)[C@H:9]([O:15]C(=O)C)[C@@H:8]([CH2:19][O:20]C(=O)C)[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]/[CH2:39][C:40]([OH:42])=O)=[CH:33][CH:32]=2)=[C:28]([CH:43]([CH3:45])[CH3:44])[NH:27][N:26]=1)(=O)C.Cl.NC[C:49]([NH2:51])=[O:50].O[N:53]1[C:57]2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.C(N(CC)CC)C>[C:49]([N:53]([CH3:57])[C:40]([CH2:39]/[CH:38]=[CH:37]/[C:34]1[CH:35]=[CH:36][C:31]([CH2:30][C:29]2[C:25]([O:24][C@@H:6]3[O:7][C@H:8]([CH2:19][OH:20])[C@@H:9]([OH:15])[C@H:10]([OH:11])[C@H:5]3[OH:4])=[N:26][NH:27][C:28]=2[CH:43]([CH3:45])[CH3:44])=[CH:32][CH:33]=1)=[O:42])(=[O:50])[NH2:51]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 2723639Glycinamide hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 685375513-(2,3,4,6-Tetra-O-acetyl-beta-D-glucopyranosyloxy)-4-({4-[(1E)-3-carboxyprop-1-enyl]phenyl}methyl)-5-isopropyl-1H-pyrazole

Product 1

HCID 685392934-({4-[(1E)-3-(carbamoyl-methylcarbamoyl)prop-1-enyl]phenyl}methyl)-3-(beta-D-gluco-pyranosyloxy)-5-isopropyl-1H-pyrazoleYield 10.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 3-(2,3,4,6-tetra-O-acetyl-β-D-gluco-pyranosyloxy)-4-({4-[(1E)-3-carboxyprop-1-enyl]phenyl}-methyl)-5-isopropyl-1H-pyrazole (0.34 g) in N,N-dimethyl-formamide (1 mL) were added glycinamide hydrochloride (0.12 g), 1-hydroxybenzotriazole (0.09 g), 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide hydrochloride (0.15 g) and triethylamine (0.27 g), and the mixture was stirred at room temperature overnight. The insoluble material was removed by filtration. To the filtrate was added 5 mol/L aqueous sodium hydroxide solution (0.5 mL), and the mixture was stirred at room temperature for 1 hour. The insoluble material was removed by filtration, and the filtrate was purified by preparative reverse phase column chromatography (Shiseido CAPCELL PAK UG120 ODS, 5 μm, 120 Å, 20×50 mm, flow rate 30 mL/minute linear gradient, water/acetonitrile=90/10-10/90) to give 4-({4-[(1E)-3-(carbamoyl-methylcarbamoyl)prop-1-enyl]phenyl}methyl)-3-(β-D-gluco-pyranosyloxy)-5-isopropyl-1H-pyrazole (0.03 g). This material was dissolved in methanol (1 mL). To the solution was added 10% palladium-carbon powder (0.01 g), and the mixture was stirred at room temperature under a hydrogen atmosphere for 3 hours. The insoluble material was removed by filtration, and the solvent of the filtrate was removed under reduced pressure to give the title compound (0.02 g).

Workup

  1. customThe insoluble material was removed by filtration
  2. additionTo the filtrate was added 5 mol/L aqueous sodium hydroxide solution (0.5 mL)
  3. stirringthe mixture was stirred at room temperature for 1 hour
  4. customThe insoluble material was removed by filtration
  5. customthe filtrate was purified by preparative reverse phase column chromatography (Shiseido CAPCELL PAK UG120 ODS, 5 μm, 120 Å, 20×50 mm, flow rate 30 mL/minute linear gradient, water/acetonitrile=90/10-10/90)

Sources & evidence

ORD record
ord-cb45a3e5e93748d29c640f809dc662d7
Source dataset
uspto-grants-2010_02
Patent number
US07655632B2

Reaction notes

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