Hydrochloric Acid → HCID 86614393, compound

HRID 1673314Notes

Reaction equation

HRID 1673314 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][C:13]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23](=[O:28])[C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:18][CH:17]=3)=[C:8]2[C:7]([O:29][C@@H:30]2[O:56][C@H:55]([CH2:57][O:58][C:59](=[O:64])[C:60]([CH3:63])([CH3:62])[CH3:61])[C@@H:47]([O:48][C:49](=[O:54])[C:50]([CH3:53])([CH3:52])[CH3:51])[C@H:39]([O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43])[C@H:31]2[O:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])=[N:6]1.[CH2:65]([O:72][CH:73]([N:77]=[C:78]=O)C(O)=O)[C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1.[OH:80]N1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.CN(C)[CH:105]=[O:106]>C(N(CC)CC)C>[CH2:65]([O:72][C:73]([NH:77][CH2:78][C:105]([NH:1][CH2:2][CH2:3][CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][C:13]([CH2:14][CH2:15][C:16]3[CH:17]=[CH:18][C:19]([O:22][C:23](=[O:28])[C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:20][CH:21]=3)=[C:8]2[C:7]([O:29][C@@H:30]2[O:56][C@H:55]([CH2:57][O:58][C:59](=[O:64])[C:60]([CH3:63])([CH3:62])[CH3:61])[C@@H:47]([O:48][C:49](=[O:54])[C:50]([CH3:53])([CH3:52])[CH3:51])[C@H:39]([O:40][C:41](=[O:46])[C:42]([CH3:43])([CH3:44])[CH3:45])[C@H:31]2[O:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:35])[CH3:36])=[N:6]1)=[O:106])=[O:80])[C:66]1[CH:67]=[CH:68][CH:69]=[CH:70][CH:71]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67340905HCID 67340905, compoundHCID 86614394HCID 86614394, compound

Product 1

HCID 86614393HCID 86614393, compound

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a solution of 1-(3-aminopropyl)-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-4-[2-(4-pivaloyloxy-phenyl)ethyl]-1H-pyrazolo[3,4-b]pyridine (60 mg) in N,N-dimethylformamide (3 mL) were added 2-benzyloxy-carbonylaminoacetic acid (17 mg), 1-hydroxybenzotriazole (11 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (26 mg) and triethylamine (0.037 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into 0.5 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. 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=1/2-1/5) to give 1-{3-[2-(benzyloxycarbonylamino)acetylamino]propyl}-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-4-[2-(4-pivaloyloxyphenyl)ethyl]-1H-pyrazolo[3,4-b]pyridine (48 mg). This material was dissolved in methanol (2 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 3 hours. The insoluble material was removed by filtration, and the solvent of the filtrate was removed under reduced pressure to give 1-[3-(2-aminoacetylamino)propyl]-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-4-[2-(4-pivaloyloxyphenyl)-ethyl]-1H-pyrazolo[3,4-b]pyridine (39 mg). This material was dissolved in methanol (2 mL). To the solution was added sodium methoxide (28% methanol solution, 0.02 mL), and the mixture was stirred at 50° C. 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) and preparative reverse phase column chromatography (Shiseido CAPCELL PAK UG120 ODS, 5 μm, 120 Å, 20×50 mm, flowrate 30 mL/minute linear gradient, water/methanol=90/10-10/90) successively to give the title compound (6 mg)

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. washThe extract was washed with water
  3. dry with materiala saturated aqueous sodium hydrogen carbonate solution and brine successively, and dried 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=1/2-1/5)

Sources & evidence

ORD record
ord-12225c35d0024691a2b4477cbae9e877
Source dataset
uspto-grants-2011_08
Patent number
US07998975B2

Reaction notes

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