Sodium Iodide → 1-(3-benzyloxycarbonylpropyl)-3-(beta-D-glucopyranosyloxy)-4-[2-(4-pivaloyloxyphenyl)ethyl]-1H-pyrazolo[3,4-b]pyridine

HRID 1673308Notes

Reaction equation

HRID 1673308 reaction equation
C([O:7][C@@H:8]1[C@@H:13]([O:14]C(=O)C(C)(C)C)[C@H:12]([O:21]C(=O)C(C)(C)C)[C@@H:11]([CH2:28][O:29]C(=O)C(C)(C)C)[O:10][C@H:9]1[O:36][C:37]1[C:45]2[C:40](=[N:41][CH:42]=[CH:43][C:44]=2[CH2:46][CH2:47][C:48]2[CH:53]=[CH:52][C:51]([O:54][C:55](=[O:60])[C:56]([CH3:59])([CH3:58])[CH3:57])=[CH:50][CH:49]=2)[NH:39][N:38]=1)(=O)C(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:68][CH2:69][CH2:70][C:71]([O:73][CH2:74][C:75]1[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1)=[O:72].[I-].[Na+]>CC(C)=O>[CH2:74]([O:73][C:71]([CH2:70][CH2:69][CH2:68][N:39]1[C:40]2=[N:41][CH:42]=[CH:43][C:44]([CH2:46][CH2:47][C:48]3[CH:49]=[CH:50][C:51]([O:54][C:55](=[O:60])[C:56]([CH3:59])([CH3:58])[CH3:57])=[CH:52][CH:53]=3)=[C:45]2[C:37]([O:36][C@@H:9]2[O:10][C@H:11]([CH2:28][OH:29])[C@@H:12]([OH:21])[C@H:13]([OH:14])[C@H:8]2[OH:7])=[N:38]1)=[O:72])[C:75]1[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 3832489Benzyl 4-bromobutanoateHCID 673408983-(2,3,4,6-Tetra-O-pivaloyl-beta-D-glucopyranosyloxy)-4-[2-(4-pivaloyloxyphenyl)ethyl]-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 673418181-(3-benzyloxycarbonylpropyl)-3-(beta-D-glucopyranosyloxy)-4-[2-(4-pivaloyloxyphenyl)ethyl]-1H-pyrazolo[3,4-b]pyridineYield 101.8%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of benzyl alcohol (1 mL) and triethylamine (2.69 mL) in dichloromethane (15 mL) was added 4-bromobutyryl chloride (1.68 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with diethyl ether. The extract was washed with water, a saturated aqueous sodium hydrogen carbonate solution and brine successively, 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=8/1) to give benzyl 4-bromobutyrate (2.45 g). To a solution of 3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-4-[2-(4-pivaloyloxyphenyl)ethyl]-1H-pyrazolo[3,4-b]pyridine (0.17 g) in acetone (3 mL) were added cesium carbonate (0.16 g), benzyl 4-bromobutyrate (0.1 g) and a catalytic amount of sodium iodide, and the mixture was stirred at room temperature for 2 days. The reaction mixture was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=10/1-3/1) to give 1-(3-benzyloxycarbonylpropyl)-3-(β-D-glucopyranosyloxy)-4-[2-(4-pivaloyloxyphenyl)ethyl]-1H-pyrazolo[3,4-b]pyridine (0.14 g). This material was dissolved in tetrahydrofuran (5 mL). To the solution was added 10% palladium-carbon powder (50 mg), and the mixture was stirred at room temperature under a hydrogen atmosphere for 3 hours. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/2-dichloromethane/methanol=15/1) to give the title compound (95 mg).

Workup

  1. customThe reaction mixture was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=10/1-3/1)

Sources & evidence

ORD record
ord-d0299d8ddd54433494879e7e4457391f
Source dataset
uspto-grants-2011_08
Patent number
US07998975B2

Reaction notes

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