Sodium Hydroxide → 1-Isopropyl-4-(4-methoxyphenylmethyl)-5-[4-(N,N-dimethyl-amino)phenyl)-3-(beta-D-glucopyranosyloxy)-1H-pyrazole

HRID 1365053Notes

Reaction equation

HRID 1365053 reaction equation
Cl.[CH3:2][N:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:15]([CH:16]([CH3:18])[CH3:17])[NH:14][C:13](=[O:19])[C:12]=2[CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)=[CH:7][CH:6]=1)[CH3:4].CC([O:32][CH2:33][C@H:34]1[O:39][C@H:38](Br)[C@H:37]([O:41]C(C)=O)[C@@H:36]([O:45]C(C)=O)[C@@H:35]1[O:49]C(C)=O)=O.[OH-].[Na+]>ClCCl>[CH:16]([N:15]1[C:11]([C:8]2[CH:9]=[CH:10][C:5]([N:3]([CH3:2])[CH3:4])=[CH:6][CH:7]=2)=[C:12]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=2)[C:13]([O:19][C@@H:38]2[O:39][C@H:34]([CH2:33][OH:32])[C@@H:35]([OH:49])[C@H:36]([OH:45])[C@H:37]2[OH:41])=[N:14]1)([CH3:17])[CH3:18]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 101776alpha-D-Glucopyranosyl bromide, tetraacetateHCID 669710015-[4-(N,N-Dimethylamino)phenyl]-1-isopropyl-4-(4-methoxyphenyl)methyl-3H-pyrazole-3-on hydrochloride

Product 1

HCID 578024031-Isopropyl-4-(4-methoxyphenylmethyl)-5-[4-(N,N-dimethyl-amino)phenyl)-3-(beta-D-glucopyranosyloxy)-1H-pyrazoleYield 59.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 5-[4-(N,N-dimethylamino)phenyl]-1-isopropyl-4-(4-methoxyphenyl)methyl-3H-pyrazole-3-on hydrochloride (0.051 g), acetobromo-α-D-glucose (0.16 g) and benzyl(n-tributyl) ammonium chloride (0.12 g) in dichloromethane (3 mL) was added sodium hydroxide (2 mol/L, 0.19 mL), and the mixture was stirred at room temperature for 3 hours. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on aminopropylated silica gel (eluent: ethyl acetate). The obtained semi purified 1-isopropyl-4-(4-methoxyphenylmethyl)-5-[4-(N,N-dimethyl-amino)phenyl]-3-(2,3,4,6-tetraacetyl-β-D-glucopyranosyloxy)-1H-pyrazole was dissolved in methanol, and sodium methoxide (28% methanol solution, 0.02 mL) was added to the solution. The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was purified by preparative reverse phase column chromatography (Shiseido CAPSELLPAC C18 UG80, 5 μM, 20×50 mm, flow rate 30 mL/min linear gradient, water/methanol=90/10-10/90) to give the title compound (0.040 g).

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate
  2. washthe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was purified by column chromatography on aminopropylated silica gel (eluent: ethyl acetate)
  6. customThe obtained semi purified 1-isopropyl-4-(4-methoxyphenylmethyl)-5-[4-(N,N-dimethyl-amino)phenyl]-3-(2,3,4,6-tetraacetyl-β-D-glucopyranosyloxy)-1H-pyrazole
  7. dissolutionwas dissolved in methanol
  8. additionsodium methoxide (28% methanol solution, 0.02 mL) was added to the solution
  9. stirringThe mixture was stirred at room temperature for 1 hour
  10. concentrationThe reaction mixture was concentrated under reduced pressure
  11. customthe residue was purified by preparative reverse phase column chromatography (Shiseido CAPSELLPAC C18 UG80, 5 μM, 20×50 mm, flow rate 30 mL/min linear gradient, water/methanol=90/10-10/90)

Sources & evidence

ORD record
ord-753c8398682a42a3aca43cd5feca88df
Source dataset
uspto-grants-2011_02
Patent number
US07888487B2

Reaction notes

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