Hydrochloric Acid → 4-[(4-{3-[N-Benzyloxycarbonyl-N-(2-carbamoylethyl)amino]-propoxy}-2-methylphenyl)methyl]-5-isopropyl-3-(2,3,4,6-tetra-O-pivaloyl-beta-D-glucopyranosyloxy)-1H-pyrazole

HRID 2189408Notes

Reaction equation

HRID 2189408 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([O:17][C@@H:18]3[O:44][C@H:43]([CH2:45][O:46][C:47](=[O:52])[C:48]([CH3:51])([CH3:50])[CH3:49])[C@@H:35]([O:36][C:37](=[O:42])[C:38]([CH3:41])([CH3:40])[CH3:39])[C@H:27]([O:28][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31])[C@H:19]3[O:20][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])=[N:11][NH:12][C:13]=2[CH:14]([CH3:16])[CH3:15])=[C:4]([CH3:53])[CH:3]=1.[CH2:54]([O:61][C:62]([N:64]([CH2:69][CH2:70][C:71]([NH2:73])=[O:72])[CH2:65][CH2:66][CH2:67]Br)=[O:63])[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1.[OH-].[Na+].Cl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl>[CH2:54]([O:61][C:62]([N:64]([CH2:65][CH2:66][CH2:67][O:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([O:17][C@@H:18]3[O:44][C@H:43]([CH2:45][O:46][C:47](=[O:52])[C:48]([CH3:51])([CH3:50])[CH3:49])[C@@H:35]([O:36][C:37](=[O:42])[C:38]([CH3:39])([CH3:41])[CH3:40])[C@H:27]([O:28][C:29](=[O:34])[C:30]([CH3:31])([CH3:32])[CH3:33])[C@H:19]3[O:20][C:21](=[O:26])[C:22]([CH3:25])([CH3:23])[CH3:24])=[N:11][NH:12][C:13]=2[CH:14]([CH3:16])[CH3:15])=[C:4]([CH3:53])[CH:3]=1)[CH2:69][CH2:70][C:71](=[O:72])[NH2:73])=[O:63])[C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 574839273-[N-Benzyloxycarbonyl-N-(3-bromopropyl)amino]propionamideHCID 685373584-[(4-Hydroxy-2-methylphenyl)methyl]-5-isopropyl-3-(2,3,4,6-tetra-O-pivaloyl-beta-D-glucopyranosyloxy)-1H-pyrazole

Product 1

HCID 866020324-[(4-{3-[N-Benzyloxycarbonyl-N-(2-carbamoylethyl)amino]-propoxy}-2-methylphenyl)methyl]-5-isopropyl-3-(2,3,4,6-tetra-O-pivaloyl-beta-D-glucopyranosyloxy)-1H-pyrazoleYield 77.7%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-[(4-hydroxy-2-methylphenyl)methyl]-5-isopropyl-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-pyrazole (0.4 g), 3-[N-benzyloxycarbonyl-N-(3-bromopropyl)amino]propionamide (0.28 g) and tetra(n-butyl)ammonium bromide (87 mg) in dichloromethane (4 mL) was added 5 mol/L aqueous sodium hydroxide solution (0.32 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with diethylether. The extract was washed with 1 mol/L hydrochloric acid, water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/3-1/6) to give the title compound (0.42 g).

Workup

  1. extractionthe resulting mixture was extracted with diethylether
  2. washThe extract was washed with 1 mol/L hydrochloric acid, water and 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 silica gel (eluent: n-hexane/ethyl acetate=1/3-1/6)

Sources & evidence

ORD record
ord-863a9fc9e4064da884136c3c80f9b0f3
Source dataset
uspto-grants-2012_12
Patent number
US08324176B2

Reaction notes

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