Hydrochloric Acid → HCID 86614398, compound

HRID 1673323Notes

Reaction equation

HRID 1673323 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[C:16]([O:32][C@@H:33]2[O:59][C@H:58]([CH2:60][O:61][C:62](=[O:67])[C:63]([CH3:66])([CH3:65])[CH3:64])[C@@H:50]([O:51][C:52](=[O:57])[C:53]([CH3:56])([CH3:55])[CH3:54])[C@H:42]([O:43][C:44](=[O:49])[C:45]([CH3:48])([CH3:47])[CH3:46])[C@H:34]2[O:35][C:36](=[O:41])[C:37]([CH3:40])([CH3:39])[CH3:38])=[N:17][N:18]3[CH2:23][CH2:24][O:25][C:26](=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28])=[CH:8][CH:7]=1.C(N(CC)CC)C.[CH3:75][S:76](Cl)(=[O:78])=[O:77].Cl>ClCCl>[CH3:75][S:76]([O:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[C:16]([O:32][C@@H:33]2[O:59][C@H:58]([CH2:60][O:61][C:62](=[O:67])[C:63]([CH3:66])([CH3:65])[CH3:64])[C@@H:50]([O:51][C:52](=[O:57])[C:53]([CH3:56])([CH3:55])[CH3:54])[C@H:42]([O:43][C:44](=[O:49])[C:45]([CH3:46])([CH3:47])[CH3:48])[C@H:34]2[O:35][C:36](=[O:41])[C:37]([CH3:38])([CH3:40])[CH3:39])=[N:17][N:18]3[CH2:23][CH2:24][O:25][C:26](=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28])=[CH:8][CH:7]=1)(=[O:78])=[O:77]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 86614399HCID 86614399, compound

Product 1

HCID 86614398HCID 86614398, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-{2-[4-(3-hydroxypropoxy)phenyl]-ethyl}-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1-(2-pivaloyloxyethyl)-1H-indazole (1.59 g) and triethylamine (0.35 mL) in dichloromethane (10 mL) was added methanesulfonyl chloride (0.16 mL), and the mixture was stirred at room temperature for 1 hour. 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 to give 4-{2-[4-(3-methane-sulfonyloxypropoxy)phenyl]ethyl}-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1-(2-pivaloyloxyethyl)-1H-indazole (1.67 g). The obtained compound (0.52 g) was dissolved in a mixed solvent of acetonitrile (2.5 mL) and ethanol (2.5 mL). To the solution were added 2-amino-1,3-propanediol (0.12 g) and sodium iodide (77 mg), and the mixture was stirred at 75° C. for 24 hours. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with 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: dichloromethane/methanol=20/1-10/1-8/1) to give 4-[2-(4-[3-[2-hydroxy-1-(hydroxymethyl)ethylamino]propoxy]-phenyl)ethyl]-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1-(2-pivaloyloxyethyl)-1H-indazole (0.36 g). This material was dissolved in methanol (6 mL). To the solution was added lithium hydroxide monohydrate (75 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 (0.21 g).

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

Sources & evidence

ORD record
ord-143bff79fc9a4f8d97fc156fed88b775
Source dataset
uspto-grants-2011_08
Patent number
US07998975B2

Reaction notes

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