Hydrochloric Acid → HCID 67343712, compound

HRID 1673328Notes

Reaction equation

HRID 1673328 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][N:11]1[C:19]2[C:14](=[C:15](Br)[CH:16]=[CH:17][CH:18]=2)[C:13]([O:21][C@@H:22]2[O:48][C@H:47]([CH2:49][O:50][C:51](=[O:56])[C:52]([CH3:55])([CH3:54])[CH3:53])[C@@H:39]([O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43])[C@H:31]([O:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])[C@H:23]2[O:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])=[N:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br-].[CH2:58]([Zn+])[C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1.Cl>O1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:58]([C:15]1[CH:16]=[CH:17][CH:18]=[C:19]2[C:14]=1[C:13]([O:21][C@@H:22]1[O:48][C@H:47]([CH2:49][O:50][C:51](=[O:56])[C:52]([CH3:55])([CH3:54])[CH3:53])[C@@H:39]([O:40][C:41](=[O:46])[C:42]([CH3:43])([CH3:44])[CH3:45])[C@H:31]([O:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:35])[CH3:36])[C@H:23]1[O:24][C:25](=[O:30])[C:26]([CH3:27])([CH3:28])[CH3:29])=[N:12][N:11]2[CH2:10][CH2:9][O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 67340912HCID 67340912, compoundHCID 178419772HCID 178419772, compound

Product 1

HCID 67343712HCID 67343712, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of 1-(2-benzyloxyethyl)-4-bromo-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-indazole (0.17 g) and tetrakis(triphenylphosphine)palladium (0) (12 mg) in tetrahydrofuran (2 mL) was added benzylzinc bromide (0.5 mol/L tetrahydrofuran solution, 0.8 mL), and the mixture was stirred at 60° C. under an argon atmosphere overnight. The reaction mixture was poured into 0.5 mol/L hydrochloric acid, and the resulting mixture was extracted with diethyl ether. The extract was washed with water and brine, 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: n-hexane/ethyl acetate=5/1-5/2) to give 4-benzyl-1-(2-benzyloxyethyl)-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-indazole (40 mg). This material was dissolved in ethyl acetate (3 mL). To the solution was added 10% palladium-carbon powder (20 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 4-benzyl-1-(2-hydroxyethyl)-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-indazole (32 mg). This material was dissolved in methanol (0.5 mL)-tetrahydrofuran (0.5 mL). To the solution was added lithium hydroxide monohydrate (9 mg), and the mixture was stirred at room temperature overnight. 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 the title compound (15 mg).

Workup

  1. extractionthe resulting mixture was extracted with diethyl ether
  2. washThe extract was washed with water and brine
  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: n-hexane/ethyl acetate=5/1-5/2)

Sources & evidence

ORD record
ord-d7998f7988c04b08b53d7476a21a84d0
Source dataset
uspto-grants-2011_08
Patent number
US07998975B2

Reaction notes

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